Differential activation by some 2-aminotetralin derivatives of the receptor mechanisms in the nucleus accumbens of rats which mediate hyperactivity and stereotyped biting.

A series of 2-aminotetralin derivatives were injected into the nucleus accumbens of rat to assess the nature of the dopamine mechanisms in this nucleus which modulate hyperactivity and stereotyped behaviour. It was shown that (1) Derivatives with either 5,6- or 6,7-dihydroxy substitutions were each able to induce hyperactivity and stereotyped behaviour, but substitutions in the 5,6-positions conferred greater potency throughout the series. This differential was emphasised by the continued activity of 2-amino-5,6-dihydroxytetralin in the absence of nialamide whilst the action of 2-amino-6,7-dihydroxytetralin was greatly reduced. (2) The hydroxyl functions in both the 5,6- and 6,7-series were essential for activity: dimethyoxy derivatives were inactive. (3) Generally, substitution of the nitrogen atom with one or two methyl groups, or with a butyl group, reduced or abolished activity. However, N-ethyl and N-propyl substitution markedly enhanced stereotypic potential in the 5,6-dihydroxy series (but not in the 6,7-series). The N-isopropyl derivative in the 5,6-series reflected the activity of the N-propyl compound but a further substitution of the N atom with the methyl group (N-isopropyl-N-methyl) greatly reduced the stereotypic potential without modification of the hyperactivity response. In contrast, N,N-dipropyl substitution abolished the hyperactivity response whilst increasing sterotypic potential. (4) alpha and beta-adrenoceptor blocking agents and alpha-methyl-p-tyrosine failed to reduce the hyperactivity induced by 2-amino-5,6-dihydroxytetralin or the stereotyped behaviour induced by 2-(N,N-dipropyl)-amino-5,6-dihydroxytetralin. Both behaviours were, however, very sensitive to blockade by haloperidol, indicating that both the hyperactivity and stereotyped responses are dopamine-dependent. It is concluded that the dopamine mechanisms in the nucleus accumbens which mediate/regulate hyperactivity and stereotyped behaviour are different. Further, it is suggested that the 2-aminotetralins may be valuable tools in studies designed to assess the topography of cerebral dopamine systems.