Abstract:
- It has been observed that agents with agonist activity at 5-HT2A receptors prevent neurotoxicity induced by the non-competitive NMDA antagonist, dizocilpine (MK-801).
- Subsequent behavioral studies reported complete antagonism by LSD and DOM of the stimulus effects of the related NMDA antagonist, phencyclidine [PCP].
- The present study sought to extend those observations to include other psychoactive drugs. Male F-344 rats were trained in a 2-lever, fixed-ratio 10, food-reinforced task with PCP (3.0 mg/kg; IP; 30 min pretreatment) as a discriminative stimulus.
- Tests of generalization were then conducted using the training dose of PCP in combination with a range of doses of DOM, LSD, d-amphetamine, MDMA, psilocybin, buspirone, and GHB.
- All of the drugs tested in combination with PCP produced a statistically significant diminution of PCP-appropriate responding but for none was antagonism complete.
- These data, obtained using a stimulus control model of the hallucinogenic effects of PCP, fail to support the hypothesis that LSD and DOM completely antagonize stimulus control by PCP.
- Instead, the data suggest complex interactions between PCP-induced stimulus control and a variety of psychoactive drugs including GHB, an agent with no known affinity for serotonergic receptors.
Keywords: Lysergic acid diethylamide (LSD); Phencyclidine (PCP); (−)-2,5-dimethoxy-4- methylamphetamine (DOM); d-amphetamine; Methylenedioxymethamphetamine (MDMA); Psilocybin; Buspirone; Gamma-hydroxybutyrate (GHB); Drug discrimination; Rat
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