Do antidepressants induce dopamine autoreceptor subsensitivity?

Macneil, Donald A.; Gower, Marie

doi:10.1038/298302a0

Cited by 24 publications

(4 citation statements)

References 2 publications

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“…However, the findings of Serra et al (1979) and Chiodo and Antelman (1980) are controversial. It was not possible to demonstrate the anti-apomorphine effect behaviourally using desipramine (Stryraki and Fibiger, 1981), imipramine and citalopram (Maj et al, 1984 b), or electrophysiologically using imipramine or amitriptyline (MacNeil and Gower, 1982;Welch et al, 1982).…”

Section: Discussionmentioning

confidence: 96%

Repeated treatment with antidepressant drugs increases the behavioural response to apomorphine

Rogóż

Skuza

et al. 1984

J. Neural Transmission

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The effect of repeated treatment (twice a day for 14 days) with antidepressant drugs (AD): imipramine, amitriptyline, zimelidine, citalopram and mianserin on the behavioural response to apomorphine in rats (open field test) was investigated. AD studied, given alone in a single dose or repeatedly, do not change the rats behaviour. A repeated but not single-dose treatment with AD facilitates the behaviour stimulation induced by apomorphine. This facilitation is observed 2 hours after the last dose of imipramine, zimelidine, citalopram and mianserin but 72 hours after the last dose of amitriptyline. The results presented suggest that the AD given repeatedly are able to increase the responsiveness of the brain DA system, probably the mesolimbic one.

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Section: Discussionmentioning

confidence: 96%

Repeated treatment with antidepressant drugs increases the behavioural response to apomorphine

Rogóż

Skuza

et al. 1984

J. Neural Transmission

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“…Accordingly, Chiodo & Antelman (1980 a) found that chronic but not acute imipramine, amitriptyline and iprindole antagonized the inhibition of DA neuron firing caused by low doses of apomorphine in the zona compacta of the substantia nigra. Other biochemical and electrophysiological studies, however, have failed to confirm these findings (Holcomb et al 1982;MacNeil & Gower, 1982;Welch et al 1982).…”

Section: Effect Of Ad On Dopamine Transmissionmentioning

confidence: 94%

Biochemical hypotheses on antidepressant drugs: a guide for clinicians or a toy for pharmacologists?

Garattini

Samanin

1988

Psychol. Med.

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SynopsisThe development of knowledge about the mechanism of action of tricyclic and the so-called ‘atypical’ antidepressants (AD) is reviewed. The discovery of clinically active antidepressants with little or no effect on noradrenaline or serotonin uptake has disproved the widely accepted concept that inhibition of monoamine uptake is a prerequisite for antidepressant activity. Another serious objection to this hypothesis is that blockade of monoamine uptake occurs in a matter of minutes after administration while 2–3 weeks of repeated treatment are necessary for the clinical AD effect. Nevertheless, the effect of repeated treatment with AD is compatible with the hypothesis that changes in central monoamine transmission are involved in the clinical activity of these drugs. Major changes in monoamine function after repeated treatment with AD include: desensitization and reduced density of noradrenaline receptors coupled to the adenylcyclase system, opposite changes in the sensitivity of α1 (increased) and α2-adrenoreceptors (decreased), down regulation of serotonin2 receptors and complex changes in the behavioural and electrophysiological responsiveness to serotonin agonists, subsensitivity of presynaptic dopamine receptors and enhanced activity of the mesolimbic dopamine system, decreased and increased density of GABA-A and GABA-B receptors respectively and down regulation of [3H]benzodiazepine binding.It remains to be clarified whether some of these changes have larger roles than others or whether they all contribute to the AD activity. An important role of dopamine in the activity of AD drugs is suggested by findings in the forced swimming test, whereas both catecholamines seem to be involved in the attenuation of escape deficit provoked by inescapable shock (learned helplessness). No clear evidence for a role of serotonin (with the possible exception of serotonin1A receptors) or GABA has been obtained in these experimental models of depression. The general validity of these findings obviously rests on the assumption that these models represent significant aspects of human depression.

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“…There is also evidence that chronic antidepressant treatment including imipramine may reduce the inhibitory effects of dopamine autoreceptor stimulation (Serra et al, 1979;Chiodo and Antelman, 1980) which results in increased dopaminergic stimulation in the striatum. This autoreceptor subsensitivity has however been queried by Welch et al (1982), MacNiell and Gower (1982) and Holcomb et al (1982) who failed to replicate the results. Spyraki and FiNger (1981) have shown an increased sensitivity of mesolimbic postsynaptic D 2 dopamine receptors following antidepressant administration.…”

Section: Discussionmentioning

confidence: 93%

Paraganglionic cell response to chronic imipramine and handling stress: an ultrastructural study

Folan

Johansson

Heym

1990

J. Neural Transmission

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The ultrastructure and connectivity of monoamine-storing paraganglionic cells in the rat superior cervical ganglion were investigated following chronic treatment with imipramine (Tofranil, Ciba-Geigy) and compared with uninjected unhandled controls and saline injected animals. The study reveals a significant decrease in the number of dense core vesicles in the drug-treated group (P less than 0.001) which is regarded as a specific effect due to receptor blocking actions of imipramine. A significant reduction in the maximum diameter of the external rim and internal cores of the vesicles (P less than 0.05) in the drug-treated group is mimicked to a certain extent by saline injections, indicating a mixed effect of stress handling and specific alteration. Although the paraganglionic cell morphology is unaltered in the group comparisons, the interrelationship of the paraganglionic cells to surrounding neural processes is significantly altered in both the control versus saline and the control versus drug group comparisons (P less than 0.05). The drug- and saline-induced alterations of neural connectivity may reflect stress-induced general changes demonstrating the plasticity of the paraganglionic cell population.

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Do antidepressants induce dopamine autoreceptor subsensitivity?

Cited by 24 publications

References 2 publications

Repeated treatment with antidepressant drugs increases the behavioural response to apomorphine

Repeated treatment with antidepressant drugs increases the behavioural response to apomorphine

Biochemical hypotheses on antidepressant drugs: a guide for clinicians or a toy for pharmacologists?

Paraganglionic cell response to chronic imipramine and handling stress: an ultrastructural study

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