Hyperactivity induced by tetrahydroisoquinoline derivatives injected into the nucleus accumbens

Several derivatives of tetrahydroisoquinoline were injected bilaterally into the nucleus accumbens of rat 2 h after a nialamide pretreatment and activity recorded in cages fitted with photocells. 1,2,3,4-Tetrahydroisoquinoline, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, 1,2,3,4-tetrahydro-6,7-dihydroxy-1-(3,4-dihydroxybenzyl)-isoquinoline (tetrahydropapaveroline) and 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline caused virtually no change in locomotor activity and 2-methyl-1,2,3,4-tetrahydroisoquinoline and 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline caused only modest hyperactivity responses. However, 3-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline and 3-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline were both shown to markedly increase activity in a dose-dependent manner. Of these two compounds, the 3-methyl-6,7-methylenedioxyderivatives was most active and equalled the effectiveness of dopamine. The responses to dopamine and to 3-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline were both threshold at 3.125 mug and maximum at 50 mug. Both effects developed within 1-2 h and persisted for at least 6 h. The hyperactivity induced by dopamine was antagonised in a dose-dependent manner by haloperidol: propranolol and aceperone were without effect. Similar results were obtained for these blocking agents against the responses to 3-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline and 2-methyl-1,2,3,4-tetrahydroisoquinoline but aceperone and propranolol, in addition to haloperidol, were shown to inhibit the hyperactivity induced by 3-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline.