Changes in the limbic neurotensin systems induced by dopaminergic drugs.

Single or multiple high doses of the dopamine-releasing drug, methamphetamine, induced 100-150% increases in the content of neurotensin-like immunoreactivity (NTLI) in the nucleus accumbens, but was without effect on the NTLI level in the ventral tegmental area. The increases in NTLI content in the nucleus accumbens were selectively blocked by the dopamine D-1 receptor antagonist, SCH 23390, which failed to exert any significant effect of its own in the same area. In contrast, haloperidol or the selective dopamine D-2 antagonist, sulpiride, when administered alone, significantly raised the NTLI level in the nucleus accumbens and when given concomitantly with methamphetamine, their effects on the amount of NTLI appeared to be additive. Very different patterns of response were observed in neurotensin systems associated with the mesocortical dopaminergic terminal fields of the frontal cortex and olfactory bulbs. Changes in NTLI contents occurred following only multiple doses of methamphetamine and consisted of decreases in levels of this peptide. However, like the nucleus accumbens, these methamphetamine-induced alterations were blocked completely by D-1 antagonism, while D-2 blockade appeared to be additive with the effects of methamphetamine.