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 (SN RIs) which inhibit selectively the uptake of serotonin and noradrenaline, b ut - in contrast to tricyclics - shaw no affinity for neurotransmitter rece ptors. The present study was aimed at determining whether repeated VEN (giv en twice daily for 14 days) induced adaptive changes in the a,adrenergic, d opamine and serotonin systems, similar to those reported by us earlier for tricyclic antidepressants. The results indicate that VEN potentiates the clonidine-induced aggressiven ess and the methoxamine-induced exploratory hyperactivity, both these effec ts being mediated by alpha(1)-adrenoceptors. VEN increased the hyperlocomot ion induced by D-amphetamine and (+/-)-7-OH-DPAT. Neither the apomorphine a nd quinpirole hyperlocomotion, nor the apomorphine and D-amphetamine stereo typies 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 i nduced by L-5-HTP of (+/-)DOI and the hyperthermia induced by trifluorometh ylphenylpiperazine, all those effects being mediated by 5-HT2 receptors. Re peated 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 D-3) sy stems and decreases the responsiveness of the 5-HT2 system. It may be concl uded that the lack of affinity for neurotransmitter receptors is of no impo rtance to the development of adaptive changes in the studied systems, obser ved after repeated treatment.