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The injection of neurotensin or the enkephalin analog Tyr-D-Ala-Gly- MePhe-Gly(ol) (DAMGO) into the A10 region of rats produces a motor stimulant effect that is associated with an increase in the postmortem levels of dopamine metabolites in the nucleus accumbens. These behavioral and neurochemical effects are augmented following daily administration. In vivo dialysis in the nucleus accumbens of conscious rats was used to determine if the acute and augmented behavioral responses following neurotensin or DAMGO administration are associated with an increase in extracellular dopamine concentrations. The acute injection of DAMGO produced a dose-dependent (0.03-3.3 nmol) elevation in extracellular dopamine and its metabolites in the nucleus accumbens. Neurotensin also produced a dose-related (0.1-3.3 nmol) increase in dopamine and its metabolites. The elevation in extracellular dopamine produced by DAMGO, but not by neurotensin, was positively correlated with the increase in motor activity. Following daily treatment of either neurotensin (1.0 nmol X 4 d) or DAMGO (0.03 nmol X 4 d), a significant elevation in extracellular dopamine levels occurred in the nucleus accumbens compared to an acute injection. The time course of the change in extracellular dopamine after daily injections was similar to the time course of the behavioral stimulation for both compounds. These data demonstrate that enhanced dopamine release in the nucleus accumbens mediates the acute behavioral effect of DAMGO but does not entirely explain the motor effects of neurotensin. However, enhanced dopamine release may mediate the behavioral sensitization produced by daily injection of both peptides into the A10 region.

Effect of acute and daily neurotensin and enkephalin treatments on extracellular dopamine in the nucleus accumbens