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

100%

Filip M., Antkiewicz-Michaluk L., Zaniewska M., Frankowska M., Golda A., Vetulani J., Przegalinski E.

Journal of Physiology and Pharmacology

2007

tom 58

nr 4

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.

The effect of an endogenous compound 1-methyl-1,2,3,4-tetrahydroisoquinoline on morphine-induced analgesia, dependence and neurochemical changes in dopamine metabolism in rat brain structures

84%

Wasik A., Romanska I., Antkiewicz-Michaluk L.

Journal of Physiology and Pharmacology

2007

tom 58

nr 2

1,2,3,4-Tetrahydroisoquinolines, among them the most interesting neuroprotective substance, an inhibitor of MAO, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), are endogenous compounds present in the central nervous system of mammals and humans. In this study, we investigated the effect of 1MeTIQ on morphine-induced analgesia, tolerance and abstinence syndrome as well as its effect on morphine-induced changes in dopamine metabolism in rat brain structures (nucleus accumbens, striatum, substantia nigra) using HPLC methodology. The experiments were carried out on male Wistar rats. Morphine analgesia was measured in the “hot-plate” test. To induce tolerance, morphine was given chronically (20 mg/kg i.p.) alone or following 1MeTIQ (50 mg/kg i.p.) injection. The development of dependence was assessed in the naloxone (2 mg/kg i.p.) precipitation test, after 10 days of morphine administration. The behavioral studies have shown that an endogenous compound, 1MeTIQ produced strong potentiation of morphine analgesia, prevented the development of morphine tolerance and inhibited expression of morphine abstinence syndrome in morphine-dependent rats. In neurochemical studies, we have demonstrated that 1MeTIQ antagonized morphine-induced changes in dopamine metabolism observed in rat brain structures. The main finding of this study was demonstration for the first time of an anti-abuse effect of an endogenous compound, 1MeTIQ, and its efficiency in counteracting morphine-induced addiction in the way useful from clinical point of view. The obtained results suggested a possibility of clinical application of 1MeTIQ in morphine addiction.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

2 Antkiewicz-Michaluk L.

1 Filip M.

1 Frankowska M.

1 Golda A.

1 Przegalinski E.

1 Romanska I.

1 Vetulani J.

1 Wasik A.

1 Zaniewska M.

2 2007

Wyniki wyszukiwania

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

The effect of an endogenous compound 1-methyl-1,2,3,4-tetrahydroisoquinoline on morphine-induced analgesia, dependence and neurochemical changes in dopamine metabolism in rat brain structures