Facilitation of brain stimulation reward by mesencephalic injections of neurotensin-(1-13).

The effects on brain stimulation reward of neurotensin-(1-13) microinjected at different concentrations (2.5, 5, 10 and 20 micrograms/0.5 microliters) into the ventral mesencephalic region containing mesocorticolimbic dopamine neurons were tested in 12 male rats. Neurotensin lowered the stimulation frequency required to sustain threshold levels of responding for brain stimulation reward, suggesting that this neuropeptide is involved in modulating the activity of dopamine neurons that mediate behaviors motivated by positive reinforces. The magnitude of the facilitatory effect of neurotensin on brain stimulation reward was dependent on the concentration injected and to a significant extent also on whether the peptide was administered in an ascending or a descending order of concentration. The different effects of neurotensin depending on the order of administration may suggest long-lasting effects on the responsiveness of neurotensin receptors in this region after injection of high concentrations of the peptide. Subsequent injection of morphine (2.5-5 micrograms/0.5 microliter) into the same site produced a weaker facilitation of brain stimulation reward than expected, suggesting that local damage after multiple central injections or prior injections of neurotensin itself reduced the responsiveness of dopamine neurons to opiates. Taken together, the results are consistent with data indicating that activation of neurotensin receptors in the ventral mesencephalon stimulates dopamine cell firing and axonal dopamine release in limbic terminal fields and suggest that endogenous neurotensin is involved in the control of behavior motivated by positive reinforcement.