Excitotoxic lesions of the prefrontal cortex attenuate the potentiation of amphetamine-induced locomotion by repeated neurotensin receptor activation.

This study was aimed at determining the role of prefrontal cortex neurons in the development of the potentiation of amphetamine-induced locomotor activity by repeated central injections of D-Tyr[11]neurotensin. Excitotoxic lesions of the prefrontal cortex were made by injecting bilaterally at three anterior-posterior placements 2 microg/microl of ibotenic acid. Ten days after surgery, locomotor responses to an intracerebroventricular injection of 0.18 or 18 nmol/10 microl of D-Tyr[11]neurotensin, or vehicle-saline, were measured in different groups of lesioned and sham rats. Ambulatory, non-ambulatory and vertical movements were measured for 2 h in activity cages starting immediately after the injection. This training phase was repeated on four occasions, every second day. One week after the last day of the training phase (day 14), locomotor responses to a single injection of amphetamine (0.75 mg/kg, IP) were measured in all rats. Results show that D-Tyr[11]neurotensin produced in sham animals a dose-dependent initial suppression of locomotor activity followed by an augmentation. The latter behavioral effect tended to be smaller in the lesioned rats, but not statistically different than in sham, suggesting that prefrontal cortex neurons do not play a major role in the stimulant effect of neurotensin on locomotor activity. However, sham rats pre-exposed to the high dose of D-Tyr[11]neurotensin showed stronger non-ambulatory and vertical movements than saline pre-exposed rats when tested with amphetamine; this sensitization effect was not observed in lesioned rats. The present results show that prefrontal cortex neurons are part of the neural circuitry involved in the development of amphetamine sensitization by repeated activation of central neurotensin receptors.