Characterisation of the mechanisms for hyperactivity induction from the nucleus accumbens by phenylethylamine derivatives.

A wide variety of phenylethylamine derivatives were injected bilaterally into the nucleus accumbens of rat following a nialamide pretreatment and hyperactivity was recorded. 2-Phenylethylamine was shown to induce a low intensity hyperactivity but the introduction of hydroxyl functions on to the phenyl ring at the 3- and/or 4-positions enhanced activity and m- and p-tyramine and dopamine each caused marked hyperactivity in the 3.4-25 mug dosage range. Methylation of one hydroxyl function reduced activity (3-methoxy-4-hydroxy- and 3-hydroxy-4-methoxy-phenylethylamine); 2(3,4-methylenedioxyphenyl) ethylamine was inactive. Agents with substitution of the side chain, such as noradreline, d-amphetamine and alpha-methyldopamine, were all shown to induce marked hyperactivity at doses of 1.6-25 mug. Alterations in the chain length markedly reduced activity (4-(3,4-dihydroxyphenyl) butylamine, 3,4-dihydroxybenzylamine). A variety of N-substituted compounds were shown to be potent inducers of hyperactivity from the nucleus accumbens (adrenaline, epinine, N-ethyldopamine, N-isopropyl-dopamine, isoprenaline) (0.2-25 mug). However, N-methyl-N-isopropyldopamine showed only weak activity and N,N-dimethyldopamine was inactive. All hyperactivity effects were shown to be dose-dependent. The hyperactivities induced by dopamine, noradrenaline and isoprenaline were each inhibited in a dose-dependent manner by subsequent injections of fluphenazine (1.25-25 mug) into the nucleus accumbens, although no reductions were recorded following similar injections of saline, solvent, 2% procaine, 50 mug propranolol or 50 mug piperoxan.