Morphine interacts with brain serotonergic (5-HT) systems; these systems have been implicated in morphine analgesia and dependence (see Cervo et al., 1981). The 5-HT agonist quipazine induces analgesia in rats that is attenuated by naloxone and 5-HT antagonists (Minnema et al., 1980; Samanin et al., 1976). Behavioral disruption by the hallucinogens LSD, DMT and mescaline, mediated primarily through brain 5-HT effects (Rech and Commissaris, 1982), is potentiated by naloxone and naltrexone (Commissaris et al., 1980; Ruffing and Domino, 1981) and is variably antagonized or potentiated by morphine and methadone (Ruffing and Domino, 1981). Cyclazocine causes a disruption of operant behavior similar to that of the hallucinogens which is reversed in part by nalozone and the 5-HT antagonist metergoline, and to a greater extent by the combination of maloxone and metergoline (Henck et al., 1983). These studies indicate that indole and phenethylamine hallucinogens interact to some extent with brain opioid mechanisms as well as brain 5-HT components, whereas opioid drugs influence behavior in part by actions on 5-HT systems. We have extended these drug studies in an attempt to characterize interactions with 5-HT mechanisms and to identify the various types of opioid receptors involved.
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