Effects of 1-methyl-1,2,3,4-tetrahydroisoquinoline on the behavioral effects of cocaine in rats.

The efficacy of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), a member of endogenous tetrahydroisoquinolines, in cocaine- and food-maintained responding in self-administration procedures under a fixed ratio 5 schedule of reinforcement as well as in cocaine and food seeking behaviors in male Wistar rats was examined. The effects of 1MeTIQ on cocaine discrimination and on basal locomotor activity were also assessed. In rats trained to self-administered either cocaine (0.5 mg/kg/injection) paired with the cue (light+tone) or food under a fixed ratio 5 schedule of reinforcement, 1MeTIQ (25 - 50 mg/kg) dose-dependently decreased the cocaine-maintained responding, but did not alter the food-maintained responding. 1MeTIQ (25 - 50 mg/kg) decreased the cocaine seeking behavior reinstated by a noncontingent presentation of cocaine (10 mg/kg, i.p.), but altered neither behavior reinstated by a discrete cue (tone+light) nor food-induced reinstatement. In rats trained to discriminate cocaine (10 mg/kg) from saline in water-reinforced fixed ratio 20 task, pretreatment with 1MeTIQ resulted in neither substitution nor significant alterations in the cocaine (1.25 - 10 mg/kg)-induced discriminative stimulus effects. 1MeTIQ (25 - 50 mg/kg) did not produce also a significant changes in basal horizontal activity. In conclusion, our present results outline a significance of exogenously applied 1MeTIQ in attenuating drug-evoked relapses to cocaine as well as the direct rewarding properties of cocaine (that model the cocaine-induced "high"), but not cocaine subjective effects. Moreover, a dissociation between effects of 1MeTIQ on cocaine vs. food-maintained responding was demonstrated.