Mechanism of Neurotensin Response to Methamphetamine Self Administration

Owing to the serious consequences of methamphetamine (METH) abuse, the response of neurotensin (NT) systems closely linked with striatal dopamine (DA) pathways was studied using operant conditioning and analyzing the response to self‐administration of METH by contingent lever pressing (SAM) after 4‐h sessions on 5 consecutive d (total of at least 3 mg/kg, iv). Yoked‐METH and saline (YM and YS, respectively) were compared. Results revealed that METH increased dorsal striatal NT levels in the SAM and, to a lesser extent, YM rats, as assessed 6 h after the final session, suggesting that METH self‐administration caused NT changes akin to those reported after high doses of METH administered non‐contingently. We were unable to assess directly if changes in the SAM animals were mediated by DA receptors, as both D1 (SCH23390) and D2 (eticlopride) blockade diminished lever pressing for METH. However, assuming that changes in the striatal NT systems of the YM group were mechanistically similar to those in SAM rats, we pre‐treated YM animals with either SCH23390 or eticlopride prior to each daily session. Results revealed that D1, but not D2, receptor blockade diminished METH‐mediated NT responses in the dorsal striatum, suggesting that the NT response and the associated mechanism in SAM are similar to the effects of a non‐contingent high‐dose of METH treatment. Support: DA09407, 019447, 013367, 00869, 11389, 04222, 00378