Effects of non‐contingent and contingent quipazine on heroin self‐administration in rhesus monkeys

Abstract

Selective 5‐HT receptor agonists enhance the antinociceptive effects of morphine at doses that attenuate its discriminative stimulus effects, suggesting that these compounds might enhance the therapeutic effects of opioids without enhancing their abuse liability. This study examined the effects of the 5‐HT2A receptor agonist quipazine on heroin self‐administration under two conditions: in one experiment (n=4), quipazine (0.32–3.2 mg/kg) was administered i.v. 5 min prior to a heroin (0.0032–0.1 mg/kg/infusion, i.v., FR 30) self‐administration session; in a second experiment (n=3), quipazine (0.32 mg/kg/infusion) was self‐administered alone and in combination with heroin. Non‐contingent administration of quipazine enhanced responding for saline and for small doses of heroin in 3 monkeys and attenuated responding for heroin in a fourth monkey. Quipazine alone (contingent) did not maintain responding and in combination with heroin did not clearly enhance the reinforcing effects of heroin. Increased responding for some doses of heroin in the presence of quipazine in both studies could be due to a reinstatement‐like effect of quipazine. These results provide support for the view that 5‐HT receptor agonists might enhance therapeutic effects of opioids without enhancing abuse liability. Supported by USPHS Grants R01DA05018, K05DA017918, CPF, T32DA031115, DRM.