Pharmacological effects of venlafaxine, a new antidepressant, given repeatedly, on the alpha 1-adrenergic, dopamine and serotonin systems.

Venlafaxine (VEN) is a representative of a new class of antidepressants (SNRIs) which inhibit selectively the uptake of serotonin and noradrenaline, but--in contrast to tricyclics--show no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated VEN (given twice daily for 14 days) induced adaptive changes in the alpha 1-adrenergic, dopamine and serotonin systems, similar to those reported by us earlier for tricyclic antidepressants. The results indicate that VEN potentiates the clonidine-induced aggressiveness and the methoxamine-induced exploratory hyperactivity, both these effects being mediated by alpha 1-adrenoceptors. VEN increased the hyperlocomotion induced by D-amphetamine and (+/-)-7-OH-DPAT. Neither the apomorphine and quinpirole hyperlocomotion, nor the apomorphine and D-amphetamine stereotypies were changed. VEN did not affect the behavioural syndrome induced by 8-OH-DPAT (a 5-HT1A effect), and decreased both the head twitch reaction induced by L-5-HTP or (+/-)DOI and the hyperthermia induced by trifluoromethylphenylpiperazine, all those effects being mediated by 5-HT2 receptors. Repeated VEN did not change the hypothermia evoked by oxotremorine (a central cholinergic agonist). The above results indicate that repeated VEN increases--as do tricyclics--the responsiveness of alpha 1-adrenergic and dopaminergic (mainly D3) systems and decreases the responsiveness of the 5-HT2 system. It may be concluded that the lack of affinity for neurotransmitter receptors is of no importance to the development of adaptive changes in the studied systems, observed after repeated treatment.