DISCRIMINATIVE STIMULUS PROPERTIES OF QUIPAZINE - DIRECT SEROTONERGIC MEDIATION

Rats were trained to discriminate intraperitoneal injections of quipazine (1.0 mg/kg) from saline in a two-lever drug discrimination task. After reliable levels of accuracy (> 85%) were attained, various agents which alter the functional activity of serotonergic (5-HT) neuronal systems were tested either alone or in combination with quipazine. Neither the 5-HT precursor, l-tryptophan, nor the 5-HT re-uptake inhibitors, fluoxetine and citalopram (Lu 10-171), either alone or in combination, elicited responding on the quipazine-appropriate lever. However, fenfluramine, a drug which releases endogenous 5-HT from nerve terminals, produced 84% quipazine-like responding. The dopamine (DA) agonists, apomorphine and amphetamine, did not transfer to quipazine. Of the several neurotransmitter antagonists tested, those which block 5-HT were also found to block the quipazine cue. Para-chlorophenylalanine (PCPA), which depletes central 5-HT by inhibiting its synthesis, significantly potentiated a sub-threshold dose (0.25 mg/kg) of quipazine and reduced the transfer of fenfluramine to quipazine, suggesting that quipazine exerts its discriminatory effect by directly stimulating central 5-HT receptors. Since the potent hallucinogen, d′lysergic acid diethylamide (LSD). has been shown to transfer to a relatively high dose of quipazine (2.5 mg/kg), this compound and other known hallucinogens were tested for transfer to the dose of quipazine (1.0 mg/kg) used in the present experiment. Mescaline, LSD, and psilocybin all produced strong transfers to the quipazine cue. These data suggest the possibility that quipazine may possess hallucinogenic properties. © 1979.