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Towell, Anthony D. (1984) Behavioural assays of the effects of antidepressant drug treatment on the functioning of catecholamine systems. Doctoral thesis, City of London Polytechnic.
The effects of antidepressant drugs on central beta-adrenergic and dopaminergic receptor function were investigated using the anorexic effects of low doses of amphetamine and apomorphine as assays of beta-adrenergic function and presynaptic dopamine function respectively. Anorexia was typically examined using a microstructural analysis of feeding, which was validated observationally.
Amphetamine anorexia was characterized by a decrease in eating time and an increase in eating rate. At 0.5 mg/kg both beta-adrenergic and dopaminergic antagonists reversed anorexic effects, whilst anorexia at 1.0 mg/kg was reversed by dopaminergic antagonists only. An enhancement of amphetamine anorexia was seen following acute desmethylimipramine treatment! this effect was exactly compensated for over chronic treatment, implying no net change at beta-adrenergic synapses. However, applying amphetamine intracranially showed that approximately 75% of the acute enhancement of amphetamine anorexia was mediated peripherally, suggesting an attenuation of beta-receptor function during chronic antidepressant drug treatment. Some further data suggested that an alpha-adrenergic change could also have contributed to the antidepressant drug-induced attenuation of anorexia.
Low doses of apomorphine, specific for presynaptic dopamine receptors, induced an anorexia characterized by decreases in both eating time and eating rate. The dopamine receptor antagonists haloperidol and thioridazine reversed apomorphine anorexia by reversing eating time but not eating rate. Administration of apomorphine into nuclei A9 and A10 reduced total food intake and eating time but not eating rate. These findings imply that presynaptic dopamine receptors mediate the effects of apomorphine on eating time. Acute treatment with desmethylimipramine, enhanced apomorphine anorexia. During chronic treatment the apomorphine-induced reduction in eating time was sometimes attenuated, suggesting a presynaptic dopamine receptor subsensitivity. Anorexia was also enhanced following acute desmethylimipramine treatment with intracranial administration of apomorphine. Again, there was no clear evidence of subsensitivity following chronic treatment, but some evidence for subsensitivity in nucleus A10 during withdrawal.
The significance of a reduced beta-receptor function and an increased dopamine function following chronic antidepressant drug treatment are discussed in relation to the biological basis of depression.
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