Antagonization of the behavioral activation produced by direct stimulation of forebrain dopamine receptors caused by intraaccumbens injections of neurotensin.

A number of studies have shown that intracisternal, intracerebroventricular, or direct administration of neurotensin (NT) into the nucleus accumbens (ACC) can antagonize the arousal and excitement produced by activation of the mesolimbic dopamine (DA) system of rats. This study investigated where NT acts relative to DA neurons to exert this antagonistic effect. In this study we selectively removed the majority of limbic forebrain DA terminals by bilateral administration of 6-hydroxydopamine (6-OHDA) into the anterolateral hypothalamus of desipramine-pretreated rats. The 6-OHDA-treated rats subsequently developed DA receptor supersensitivity, as evidenced by behavioral supersensitivity to L-DOPA. The L-DOPA dose employed was subthreshold for behavioral excitation in control rats. The behavioral excitation to L-DOPA in 6-OHDA-treated rats consisted of increases in sniffing and increases in locomotion and/or rearing, along with decreases in resting and sleep. Following bilateral intra-ACC injections of NT, L-DOPA-induced sniffing, rearing, and locomotion decreased significantly, and resting and sleep increased significantly. These data suggest that intra-ACC NT, acting in or proximal to the ACC, can antagonize the behavioral effects of limbic DA stimulation and that this antagonism is postsynaptic to DA neurons.