PT  - JOURNAL ARTICLE
AU  - Glen R. Hanson
AU  - Amanda J. Hoonakker
AU  - Christina M. Robson
AU  - Lisa M. McFadden
AU  - Paul S. Frankel
AU  - Mario E. Alburges
TI  - Response of Neurotensin Basal Ganglia Systems during Extinction of Methamphetamine Self-Administration in Rat
AID  - 10.1124/jpet.113.205310
DP  - 2013 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 173--181
VI  - 346
IP  - 2
4099  - http://jpet.aspetjournals.org/content/346/2/173.short
4100  - http://jpet.aspetjournals.org/content/346/2/173.full
SO  - J Pharmacol Exp Ther2013 Aug 01; 346
AB  - Because of persistent social problems caused by methamphetamine (METH), new therapeutic strategies need to be developed. Thus, we investigated the response of central nervous system neurotensin (NT) systems to METH self-administration (SA) and their interaction with basal ganglia dopamine (DA) pathways. Neurotensin is a peptide associated with inhibitory feedback pathways to nigrostriatal DA projections. We observed that NT levels decreased in rats during extinction of METH SA when lever pressing resulted in intravenous infusions of saline rather than METH. Thus, 6 h after the first session of extinction, NT levels were 53, 42, and 49% of corresponding controls in the anterior dorsal striatum, posterior dorsal striatum, and globus pallidus, respectively. NT levels were also significantly reduced in corresponding yoked rats in the anterior dorsal striatum (64% of control), but not the other structures examined. The reductions in NT levels in the anterior dorsal striatum particularly correlated with the lever pressing during the first session of extinction (r =s; 0.745). These, and previously reported findings, suggest that the extinction-related reductions in NT levels were mediated by activation of D2 receptors. Finally, administration of the neurotensin receptor 1 (NTR1) agonist [PD149163 [Lys(CH2NH)Lys-Pro,Trp-tert-Leu-Leu-Oet]; 0.25 or 0.5 mg/kg] diminished lever pressing during the first extinction session, whereas the NTR1 antagonist [SR48692 [2-[(1-(7-chloro-4-quinolinyl)-5-(2,6-imethoxyphenyl)pyrazol-3-yl)carbonylamino]tricyclo(3.3.1.1.(3.7))decan-2-carboxylic acid]; 0.3 mg/kg per administration] attenuated the reduction of lever pressing during the second to fourth days of extinction. In summary, these findings support the hypothesis that some of the endogenous basal ganglia NT systems contribute to the elimination of contingent behavior during the early stages of the METH SA extinction process.