Psychiatric Annals

Neurotransmitter Receptor Plasticity: Alterations by Antidepressants and Antipsychotics

Richard L Hauger, MD; Steven M Paul, MD

Abstract

Antidepressant and antipsychotic agents have proven clinically effective in the treatment of the major affective disorders and psychoses.' Since neurochemical studies on the mechanism(s) of action of each of these drugs are inherently difficult to carry out in man, researchers have attempted to extrapolate data derived from experiments in laboratory animals. Although antidepressant and antipsychotic agents have been shown to produce a variety of neurochemical effects it is still uncertain as to which, if any, of these actions are responsible for their therapeutic actions. Tricyclic antidepressants, for example, can potently inhibit the presynaptic uptake of norepinephrine and serotonin into monoa minergic neurons, but inhibition of reuptake occurs immediately after administration.'"4 Consequently, inhibition of neurotransmitter reuptake by tricyclic antidepressants may not account for the clinical efficacy of anti-depressants which develops over two or more weeks.5

More recently the chronic effects of antidepressants and antipsychotics on postsynaptic monoaminergic receptors have been examined. These "receptors" represent specific recognition sites or proteins that selectively bind a given neurotransmitter resulting in a subsequent biochemical or ionic event. Alterations in such receptors by various drugs may therefore represent adaptive changes brought about by drug-induced increases or decreases in neurotransmitter turnover. Alternatively drugs may have direct actions on receptor protein (or the local membrane milieu) and thereby alter the response to a given neurotransmitter. Currently methods forassessing both pre- and postsynaptic neurotransmitter receptor "sensitivity" are available. Radioligands of high specific radioactivity are used to label neurotransmitter receptor sites on neuronal membranes. By determining the number of binding sites for a given neurotransmitter receptor ligand, one can deduce whether "supersensitivity" (increased number of binding sites) or "subsensitivity" (decreased number of binding sites) occurs after drug treatment. Over the past five years, numerous studies have investigated alterations in the plasticity of neurotransmitter receptors induced by psychotropic agents. These studies and their clinical implications will be reviewed in this article.

TRICYCLIC ANTIDEPRESSANTS

The most consistent neurochemical effect observed after chronic administration of tricyclic antidepressants is a reduction in the functional activity and number of β-adrenergic receptors in the cerebral cortex of laboratory animals (Table I). Administration of various antidepressants to rats for two to six weeks leads toa marked reduction in the number of cerebral cortical β-adrenergic receptors and in the sensitivity of the adenylate cyclase (second messenger system) coupled to noradrenergic receptors in the limbic forebrain.6 This phenomena called "subsensitivity" is believed to result from an increase in the intrasynaptic concentration and turnover of norepinephrine. So far, all "classical" tricyclic antidepressants have been shown to produce β-adrenergic receptor desensitization in laboratory animals (Table I).7-10 Moreover, tricyclic antidepressant-induced desensitization of β-adrenergic receptors requires a time lag of from one to several weeks which is similar to the clinical response time seen with antidepressants. Significantly, acute treatment with these drugs does not produce β-adrenergic receptor desensitization in animals. Since chronic administration of tricyclic antidepressants does not alter a variety of other central neurotransmitter receptors such as the muscarinic-cholinergic, histaminergic, and striatal dopaminergic receptors, the reduction in β-adrenergic receptors appears to be a relatively specific action. Additionally, other adrenergic receptors including postsynaptic α1- and α2-adrenergic receptors are not consistently influenced by tricyclic antidepressants, although amitriptyiine has been reported to increase α1-adrenergic receptors in the mouse forebrain.11

Table

1. Klein DF, Gittelman R, Quitkin F, et al: Diagnosis and Drug Treatment of Psychiatric Disorders: Adults and Children. Baltimore, Williams and Wilkins Co. 1 980.

2. Glowinski J. Axelrod J: Inhibition of uptake of tritiated-noradrenaline in the intact rat brain by Imipramine and structurally related compounds. Nature 1964; 204:1318-1319.

3. Carlsson A, Corrodi H, Fuxe K, et al: Effect of antidepressant drugs on the…

Antidepressant and antipsychotic agents have proven clinically effective in the treatment of the major affective disorders and psychoses.' Since neurochemical studies on the mechanism(s) of action of each of these drugs are inherently difficult to carry out in man, researchers have attempted to extrapolate data derived from experiments in laboratory animals. Although antidepressant and antipsychotic agents have been shown to produce a variety of neurochemical effects it is still uncertain as to which, if any, of these actions are responsible for their therapeutic actions. Tricyclic antidepressants, for example, can potently inhibit the presynaptic uptake of norepinephrine and serotonin into monoa minergic neurons, but inhibition of reuptake occurs immediately after administration.'"4 Consequently, inhibition of neurotransmitter reuptake by tricyclic antidepressants may not account for the clinical efficacy of anti-depressants which develops over two or more weeks.5

More recently the chronic effects of antidepressants and antipsychotics on postsynaptic monoaminergic receptors have been examined. These "receptors" represent specific recognition sites or proteins that selectively bind a given neurotransmitter resulting in a subsequent biochemical or ionic event. Alterations in such receptors by various drugs may therefore represent adaptive changes brought about by drug-induced increases or decreases in neurotransmitter turnover. Alternatively drugs may have direct actions on receptor protein (or the local membrane milieu) and thereby alter the response to a given neurotransmitter. Currently methods forassessing both pre- and postsynaptic neurotransmitter receptor "sensitivity" are available. Radioligands of high specific radioactivity are used to label neurotransmitter receptor sites on neuronal membranes. By determining the number of binding sites for a given neurotransmitter receptor ligand, one can deduce whether "supersensitivity" (increased number of binding sites) or "subsensitivity" (decreased number of binding sites) occurs after drug treatment. Over the past five years, numerous studies have investigated alterations in the plasticity of neurotransmitter receptors induced by psychotropic agents. These studies and their clinical implications will be reviewed in this article.

TRICYCLIC ANTIDEPRESSANTS

The most consistent neurochemical effect observed after chronic administration of tricyclic antidepressants is a reduction in the functional activity and number of β-adrenergic receptors in the cerebral cortex of laboratory animals (Table I). Administration of various antidepressants to rats for two to six weeks leads toa marked reduction in the number of cerebral cortical β-adrenergic receptors and in the sensitivity of the adenylate cyclase (second messenger system) coupled to noradrenergic receptors in the limbic forebrain.6 This phenomena called "subsensitivity" is believed to result from an increase in the intrasynaptic concentration and turnover of norepinephrine. So far, all "classical" tricyclic antidepressants have been shown to produce β-adrenergic receptor desensitization in laboratory animals (Table I).7-10 Moreover, tricyclic antidepressant-induced desensitization of β-adrenergic receptors requires a time lag of from one to several weeks which is similar to the clinical response time seen with antidepressants. Significantly, acute treatment with these drugs does not produce β-adrenergic receptor desensitization in animals. Since chronic administration of tricyclic antidepressants does not alter a variety of other central neurotransmitter receptors such as the muscarinic-cholinergic, histaminergic, and striatal dopaminergic receptors, the reduction in β-adrenergic receptors appears to be a relatively specific action. Additionally, other adrenergic receptors including postsynaptic α1- and α2-adrenergic receptors are not consistently influenced by tricyclic antidepressants, although amitriptyiine has been reported to increase α1-adrenergic receptors in the mouse forebrain.11

Table

TABLE 1REGULATION OF NEUROTRANSMITTER RECEPTORS IN THE CEREBRAL CORTEX OF RATS BY CHRONIC TRICYCLIC AND ATYPICAL ANTIDEPRESSANT TREATMENT

TABLE 1

REGULATION OF NEUROTRANSMITTER RECEPTORS IN THE CEREBRAL CORTEX OF RATS BY CHRONIC TRICYCLIC AND ATYPICAL ANTIDEPRESSANT TREATMENT

The ascending serotonergic projections from the midbrain represent another important neurotransmitter system that is involved in the antidepressant action of antidepressant drugs. Serotonin receptors in the frontal cortex can be labeled with [p 3H]-spiroperidol and this subclass of serotonin receptors has been designated the 5-HT2 receptor.8 Chronic but not acute treatment with many tricyclic antidepressants reduces the density of 5-HT2 receptors in cerebral cortical areas (Table I).8 Though some tricyclic antidepressants can also reduce the other subclass of serotonergic receptors (so called 5-HT1), most antidepressants have no effect on 5-HT1 receptors.9'10 This suggests that the "desensitization" of 5-HT2 receptors may be more relevant to antidepressant activity.

Though the regulation of β-adrenergic and serotonergic (5-HT2) receptors appears to correlate temporally with the alleviation of depression by tricyclic antidepressants, a differential sensitivity to the various drugs has been reported. Desipramine, a secondary amine tricyclic agent which predominantly blocks norepinephrine reuptake, is more effective than amitriptyiine in desensitizing the β-adrenergic receptor.8,10 Conversely, amitriptyiine, a tertiary amine tricyclic antidepressant with strong selectivity for blocking serotonin reuptake, preferentially desensitizes the serotonergic (5-HT2) receptor.9 These results, coupied with clinical data on the differential response of depressed patients to either desipramine or amitriptyiine, supports the notion that a single biochemical "mechanism" may be insufficient to explain the clinical effects of all antidepressants.

Recent evidence also suggests a functional linkage between the serotonergic and noradrenergic systems in mediating the neurochemical effects of antidepressants. When the serotonergic system is destroyed by lesioning animals with the specific serotonin neurotoxin, 5,7-dihydroxytryptamine, administration of tricyclic antidepressants fails to reduce the density of β-adrenergic receptors as well as the sensitivity of β-adrenergic receptor coupled adenylate cyclase. Thus the serotonergic system plays a "permissive" role in the desensitization of β-adrenergic receptors by tricyclic antidepressants.12 Conversely destruction of the brain noradrenergic system by 6-hydroxydopamine abolishes the ability of chronic electroconvulsive treatment (ECT) to enhance serotoninmediated behaviors in rats.13 The functional linkage between serotonergic and noradrenergic neuronal system in mediating the effects of antidepressants in animals may provide a basis for unifying the two major hypotheses of affective disorders, the "serotonin" and "norepinephrine" hypotheses. Because it is now well documented that neurotransmitter systems communicate with one another it is unlikely that drugs can produce isolated effects on only one system.

The time lag in antidepressant action is a major clinical dilemma for treating patients with moderate to severe symptoms. It would be of great therapeutic benefit if this time lag could be eliminated, or reduced. Recent studies in our and other laboratories suggest that a presynaptic α2-adrenergic receptor may be involved in the postsynaptic receptor changes seen in both the β-adrenergic and serotonergic systems. Previous studies have shown that the presynaptic α2-adrenergic"autoreceptor"adjusts the neuronal firing rate to correspond to the synaptic concentration of transmitter. For example, a large concentration of norepinephrine in the synaptic cleft would result in a signal by the presynaptic α2-adrenergic receptor to decrease the neuronal firing rate and, secondarily, to decrease both the releaseand intrasynaptic concentration of norepinephrine. Thus "feedback inhibition" by presynaptic α2-adrenergic autoreceptors would theoretically retard the development of β-adrenergic receptor desensitization. If the inhibitory role of the α2-autoreceptor on norepinephrine release could somehow be eliminated so that the neuronal firing rate continued to increase as norepinephrine accumulated in the synapse, the postsynaptic β-adrenergic receptor will be exposed to higher norepinephrine concentrations and thus would desensitize sooner. Furthermore, acute treatment with some tricyclic antidepressants appears to activate presynaptic α2-autoreceptors on locus coeruleus neurons, resulting in a decrease in firing rate and attenuating the increase in norepinephrine release that is observed after chronic administration of these drugs.14

Recently, it has been shown that phenoxybenzamine, an α-adrenergic receptor blocker, added to a regimen of desipramine, produces a rapid desensitization of cerebral cortical β-adrenergic receptors within one day.15 When phenoxybenzamine and desipramine were administered chronically to rats for 12 days the resulting β-adrenergic receptor "desensitization" was greater than that observed with desipramine alone.15 Thus, α-adrenergic receptor blockers not only accelerate the time course of β-adrenergic receptor desensitization but quantitatively potentiate the effect of antidepressants on β-adrenergic receptor density. A similar rapid desensitization of cerebral cortical β-adrenergic receptors has also been demonstrated with another a-adrenergic receptor antagonist, yohimbine.16 More recently, rapid desensitization of cortical 5-HT2 receptors has been demonstrated following combined treatment with trazodone and phenoxybenzamine.17 Thus the blockade of α2-adrenergic autoreceptors clinically, may lead to more rapid recovery from depression as well as from depressions refractory to tricyclic antidepressants alone. These studies have heuristic value as well since potentiation of the mood elevating properties of tricyclic antidepressants by α-adrenergic receptor antagonists would indeed suggest that β-adrenergic and/or serotonergic receptor desensitization is involved in the mechanism of action of these drugs. Although these clinical studies have not yet been undertaken it is clear that such research in animals can quickly generate potential new treatment regimens for man.

Hormones can also induce modifications in the effects of antidepressants on the number and sensitivity of neurotransmitter receptors. ACTH, like yohimbine, is capable of accelerating the decrease in β-adrenergic receptors produced by certain antidepressants.18 This effect seems to be a direct action of this peptide in the brain rather than through release of adrenal hormones. Previous investigators have shown that adrenal steroids alone influence β-adrenergic receptors. Adrenalectomy, for example, augments the increase in β-adrenergic receptors in the rat hippocampus which occurs after 6-hydroxydopamine lesions in rats and the administration of corticosterone reverses this effect.19 Ovarian steroids have also been shown to influence neurotransmitter receptor adaptations to antidepressants. Surprisingly, ovariectomy has been reported to abolish the "down regulation" or desensitization of serotonergic (5-HT2) receptors in rat cerebral cortex produced by Imipramine.20 Administration of estradiol or progesterone separately or in combination restores the effect of chronic Imipramine administration.20 Additionally, chronic estradiol administration can reduce the number of cerebral cortical β-adrenergic receptors.21 These results suggest that hormonal changes that occur in postmenopausal women may profoundly influence the efficacy of antidepressants. Moreover, the possible therapeutic effects of hormone replacement in combination with antidepressants may need to be examined more carefully in this group of patients. Though the effects af thyroid hormone on brain neurotransmitter receptors have not been fully elucidated, the lack of circulating thyroid hormones has been shown to decrease the number of β-adrenergic receptors in the rat cerebral cortex.22 Conversely, the density of β-adrenergic receptors in rat heart is increased by administration of thyroid hormone.23 A similar phenomenon in the brain could help explain the recent finding that tri-iodothyronine (T3) can rapidly convert tricyclic antidepressant non-responders to res ponders.24

Table

TABLE 2REGULATION OF NEUROTRANSMITTER RECEPTORS IN THE CEREBRAL CORTEX SYSTEM BY CHRONIC MONOAMINE OXIDASE INHIBITOR TREATMENT

TABLE 2

REGULATION OF NEUROTRANSMITTER RECEPTORS IN THE CEREBRAL CORTEX SYSTEM BY CHRONIC MONOAMINE OXIDASE INHIBITOR TREATMENT

ATYPICAL ANTIDEPRESSANTS

Atypical antidepressants such as iprindole. trazodone, and zimelidine have also been shown to desensitize cerebral cortical β-adrenergic receptors (Table I).8,10 However, iprindole is devoid of any direct effects on biogenic amine reuptake or postsynaptic receptors, while trazodone is a selective serotonin reuptake inhibitor. The ability of iprindole to produce desensitization may involve an increase in the synaptic release of norepinephrine since destruction of presynaptic noradrenergic terminals with 6-hydroxydopamine prevents the effect of this drug on β-adrenergic receptors.25

Likewise mianserin, a tetracyclic agent without serotonin reuptake blocking ability, reduces serotonergic (5-HT2) receptor density (Table I), but does not reduce β-adrenergic receptors indicating that desensitization of the β-adrenergic and 5-HT2 receptors may be unrelated phenomena.9 Furthermore, fluoxetine, a selective serotonin reuptake inhibitor, does not reduce β-adrenergic receptor density upon chronic administration (Table I) and does not appear to be an effective antidepressant.9 Consequently, desensitization of neurotransmitter receptors by certain antidepressants appears to involve some as yet unknown presynaptic mechanisms.

Recently, alprazolam, a triazolobenzodiazepine, has been shown to be an effective antidepressant and antipanic agent. Significantly, it has been shown that alprazolam alone has no effect on β-adrenergic receptors but can prevent the increase in β-adrenergic receptor density which results from reserpine administration.26 Diazepam, which has no appreciable antidepressant activity, failed to reverse the reserpine-induced increase in β-adrenergic receptor density. Again this suggests that reduction in β-adrenergic receptors may be a common mechanism of a variety of chemically-unrelated antidepressant agents. Moreover administration of reserpine (a "depressogenic" drug in man) to rats may increase the sensitivity for detecting clinically relevant compounds in animal screening tests.

MONOAMINE OXIDASE INHIBITORS

Monoamine oxidase inhibitors also alter neurotransmitter receptors in the central nervous system.9'27 Their most consistent effect is to produce "down regulation" of /3-adrenergic receptors (Table 2). There is also evidence that certain monoamine oxidase inhibitors decrease serotonergic (both 5-HT1 and 5-HT2) receptors. Clorgyline, a selective monoamine oxidase A inhibitor, has been reported to decrease acutely (3 days) α2-adrenergic receptors and to chronically reduce α1- and β-adrenergic receptors.27 Rapid desensitization of β-adrenergic receptors by monoamine oxidase inhibitors also occurs when phenoxybenzamine is administered concomitantly.15 This suggests that the α2-adrenergic "autoreceptor" may be important in the action of both tricyclic antidepressants and monoamine oxidase inhibitors, and that the combination may be of therapeutic benefit.

Table

TABLE 3REGULATION OF NEUROTRANSMITTER RECEPTORS BY LITHIUM, ECT, AND NEUROLEPTICS

TABLE 3

REGULATION OF NEUROTRANSMITTER RECEPTORS BY LITHIUM, ECT, AND NEUROLEPTICS

ELECTROCONVULSIVE THERAPY

Chronic, but not acute, electroconvulsive treatment (ECT) in animals "down regulates" cerebral cortical β-adrenergic receptors in a similar fashion to the chemical antidepressant therapies (Table 3).28 ECT does not appear to have any effects on α1-adrenergic or α2adrenergic receptors, or muscarinic -cholinergic receptors (Table 3). Though ECT does not change the number of striatal dopaminergic receptors, it has been reported in neurophysiologic experiments to induce a subsensitivity of presynaptic dopamine autoreceptors.'9 Such an effect could reverse the inhibitory influence of the dopamine autoreceptor on dopamine release and ameliorate depression by an enhancement of dopaminergic transmission. The effects of ECT on serotonergic (5-HT2) receptors are opposite to the effects observed with tricyclic anti-depressants. Chronic ECT treatment increases 5-HT2 receptor density while tricyclic antidepressants reduce 5-HT2 receptors.30 This effect is not necessarily inconsistent with the "down regulation" produced by chemical antidepressants since, in contrast to the β-adrenergic receptor coupled adenylate cyclase, the effect of increased or decreased 5-HT2 receptor density on "functional" serotonergic neuronal responsivity is still unclear.

LITHIUM

Administration of lithium to laboratory animals also decreases cerebral cortical β-adrenergic receptors, an effect which corresponds temporally with its antidepressant effects (Table 3).31 An important effect of lithium appears to be the specific reduction of 5-HT1 and 5-HT2 serotonergic receptors in the hippocampus but not the cerebral cortex.32 Consistent with this highly localized "down regulation" of serotonin receptors, is a stimulation of serotonin release by lithium in the hippocampus.32 Thus, lithium increases serotonin release and decreases the number of postsynaptic serotonin receptors in the hippocampus. Lithium has also been reported to decrease the number of striatal dopamine and neuromuscular cholinergic receptors.'2''4 Stabilization of neurotransmitter receptor alterations may be one mechanism whereby lithium prevents recurrences in bipolar illness. In rats lithium has been reported to prevent the development of dopamine receptor supersensitivity which follows chronic neuroleptic treatment. After chronic haloperidol administration, striatal dopamine receptors are increased (Table 3). However, when animals are pretreated with lithium just prior to a regimen of haloperidol, both the behavioral "supersensitivity" to apomorphine and the increase in striatal dopamine receptors does not occur.'5 Lithium has also been reported to prevent the increase in extrajunctional acetylcholine receptors which appears following denervation of striatal muscle.34 The ability of lithium to inhibit the development of receptor supersensitivity and thus stabilize neurotransmitter receptor plasticity may explain its efficacy in manic-depressive illness.

ANTIPSYCHOTICS

The chronic effects of neuroleptics on various neurotransmitter receptors have been studied primarily in relation to the long-term neurological side effects of these agents. Nevertheless since the therapeutic effects of these drugs are also noted to increase during subacute or chronic administration, these same studies may be relevant to the antipsychotic actions of these agents. Chronic treatment of rats (1 week to 12 months) with neuroleptics increases the density of striatal (D2) receptors, dopamine receptors not associated with dopamine-sensitive adenylate cyclase (Table 3).36,37 A recent study demonstrated that, coincident with dopamine receptor supersensitivity, basal striatal acetylcholine content also increased." This provides evidence for spontaneous dopaminergic synaptic overactivity during chronic neuroleptic treatment. This finding indicates that the dopamine hypothesis of schizophrenia may have to be revised since the action of antipsychotics may be more complex than simple direct dopamine receptor blockade. Antipsychotics do not alter β-adrenergic or serotonergic (5-HT2) receptors (Table 3), therefore their antimanic properties may also involve, effects on dopaminergic neurotransmission.

CONCLUSIONS

In animals, the most consistent neurotransmitter receptor changes produced by antidepressant agents (tricyclic antidepressants, monoamine oxidase inhibitors, lithium, ECT) are "down regulation" of β-adrenergic and serotonergic (5-HT2) receptors. Consequently, "down regulation" or desensitization of these receptors may be an essential neurochemical event in the alleviation of depression seen during treatment with these drugs.

Amitriptyiine is more potent in producing 5-HT2 receptor desensitization while desipramine is more potent in producing β-adrenergic receptor desensitization. Whether these effects are responsible for the differentia] sensitivity of various depressed patients reported by some authors to these drugs is uncertain. However, since tricyclic antidepressants are not equipotent in producing a given neurochemical effect it appears reasonable to try a different "spectrum" antidepressant when treating patients who are unresponsive to one or more agents.

Blockade of α2-adrenergic autoreceptors during treatment with tricyclic antidepressants or monoamine oxidase inhibitors produces rapid desensitization of both β-adrenergic and serotonergic (5-HT2) receptors. The combined use of α2-antagonists with antidepressants may reduce the time lag of conventional antidepressant treatment and potentiate antidepressant efficacy. Similarly co-administration of thyroid or ACTH, or ovarian steroids to postmenopausal women, may enhance the antidepressant actions of these drugs. However, most of these predictions from laboratory animal studies have not been adequately studied in clinical trials.

Lithium selectively enhances hippocampal serotonergic neurotransmission and prevents or stabilizes the development of striatal dopamine receptor supersensitivity. Decreases in the plasticity of neurotransmitter receptors by lithium may underlie its therapeutic efficacy in bipolar affective illness.

Chronic administration of antipsychotics increases the number of striatal dopamine (D2) receptors which is maintained even during increased spontaneous release of dopamine. Thus, the antipsychotic actions of neuroleptics may not simply involve blockade of postsynaptic dopamine receptors.

REFERENCES

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3. Carlsson A, Corrodi H, Fuxe K, et al: Effect of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxy-tryptamine stores caused by 4-methyl-alpha-ethyl-meta tyramine. Eur J Pharmacol 1969; 5:357-366.

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12. Janowsky A, Okada F, Manier DH, et al: Role of serotonergic input in the regulation of the β-adrenergic receptor-coupled adenylate cyclase systems. Science 1982; 218:900-901.

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14. Svensson TH, Usdin T: Feed-back inhibition of brain noradrenaline neurons by tricyclics: a-receptor mediation after acute and chronic treatment. Science 1978; 202:1089-1091.

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16. Johnson RW. Reisine T, Spotnitz S, et al: Effects of desipramine and yohimbine on α- and β-adrenoreceptor sensitivity. Eur J Pharmacol 1980; 67:123-127.

17. Taylor DP. Allen LE, Ashworth EM. et al: Treatment with trazadone plus phenoxybenzamine accelerates development of decreased type 2 serotonin binding in rat cortex. Neuropharmacology 1981; 20:513-516.

18. Kendall DA. Duncan R. Stopis J. et at: Influence of adrenocorticotropin hormone and yohimbine on antidepressant-induced declines in rat brain neurotransmitter receptor binding and function. J Pharmacol Exp Therap 1982; 222:566-571.

19. Roberts DCS, Bloom FE: Adrenal steroid-induced changes in β-adrenergic receptor binding in rat hippocampus. Eur J Pharmacol 1981; 74:37-41.

20. Kendall DA, Stancel GM, Enna SJ: Imipramine: Effect of ovarian steroids on modifications in serotonin receptor binding. Science 1981; 211:1 183-1185.

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TABLE 1

REGULATION OF NEUROTRANSMITTER RECEPTORS IN THE CEREBRAL CORTEX OF RATS BY CHRONIC TRICYCLIC AND ATYPICAL ANTIDEPRESSANT TREATMENT

TABLE 2

REGULATION OF NEUROTRANSMITTER RECEPTORS IN THE CEREBRAL CORTEX SYSTEM BY CHRONIC MONOAMINE OXIDASE INHIBITOR TREATMENT

TABLE 3

REGULATION OF NEUROTRANSMITTER RECEPTORS BY LITHIUM, ECT, AND NEUROLEPTICS

10.3928/0048-5713-19830501-04

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