Phenylephrine-induced activity in mice as a model of central alpha 1-adrenoceptor function. Effects of acute and repeated administration of antidepressant drugs and electroconvulsive shock.

Intracerebroventricular injection of the alpha 1-agonists phenylephrine (10-100 micrograms) or methoxamine (10-50 micrograms) produced a dose-dependent increase in locomotor activity and behavioural excitation in mice. The syndrome induced by phenylephrine was inhibited by prazosin but not yohimbine, RX 781094 or propranolol. Methoxamine-induced responses were, however, also reduced by yohimbine. Activity induced by phenylephrine was not affected by metergoline or pirenperone but was reduced by haloperidol and spiroperidol. This latter effect, however, may have been due to inhibition of alpha 1-adrenoceptors and/or dopamine receptors. Pretreatment with alpha-methyl-p-tyrosine or FLA-63 reduced responses to phenylephrine by respectively inhibiting either the locomotor activity or the other behavioural components of the syndrome. This suggests that some residual noradrenergic and possibly also dopaminergic function may be necessary for the behavioural expression of the effects of phenylephrine. The activity was inhibited by mianserin and amitriptyline but not by desmethylimipramine. When these antidepressant drugs were given twice daily for 14 days, mianserin alone affected the activity induced by phenylephrine, tested either 12 or 60 hr after the final injection. This behaviour was also not altered 24 hr after the mice had received an electroconvulsive shock under halothane anaesthesia, once daily for 10 days. In conclusion, the data suggest that the behavioural syndrome induced by phenylephrine probably provides a specific and quantifiable assessment of central alpha 1-adrenoceptor function and that in general this is unaltered following repeated administration of antidepressant drugs or electroconvulsive shock.