The effects of neurotensin and [D-Tyr11]-NT on the hyperactivity induced by intra-accumbens administration of a potent dopamine receptor agonist

The effects of neurotensin on the strong and persistent hyperactivity induced in rats by intra-accumbens administration of ADTN, a potent dopamine agonist, were examined. Neurotensin was administered intraventricularly as well as bilaterally into the accumbens. With both routes of administration neurotensin significantly decreased the hyperactivity produced by ADTN. However, important differences in doses required to produce this effect were noted between the two routes of administration. Whereas intraventricular injection of doses as small as 0.05 micrograms neurotensin was sufficient to reduce hyperactivity, bilateral intra-accumbens administration of at least 1.8 micrograms was required to replicate the effect. ADTN induced hyperactivity was also significantly decreased by intraventricular and intra-accumbens injections of the structural analog [D-Tyr11]-NT. In both routes of administration, the inhibitory action of the analog was more persistent than that observed with neurotensin. As was the case for neurotensin, intraventricular administration of [D-Tyr11]-NT was more potent than intra-accumbens injections. Finally, the results of a preliminary experiment indicate that neurotensin injected intraventricularly can also decrease hyperactivity elicited by intra-accumbens administration of dibutyryl cyclic AMP. Taken together, the results of the present study demonstrate that neurotensin can affect hyperactivity elicited by a strong and persistent activation of mesolimbic dopamine receptors or by stimulation of events beyond these receptors. The observed greater efficacy of intraventricularly administered neurotensin in decreasing ADTN induced hyperactivity suggests an action of the peptide on regions distant from the accumbens, probably on efferent outputs of mesolimbic stimulation.