부산대학교 도서관

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1460-9568.2009.06904.x Byline: Heath D. Schmidt (1), Katie R. Famous (2), R. C. Pierce (1) Keywords: acetylcholine; dopamine; glutamate; medial prefrontal cortex; nucleus accumbens; ventral tegmental area Abstract: Abstract The direct glutamatergic projection from the medial prefrontal cortex (mPFC) to the nucleus accumbens plays a critical role in mediating the reinstatement of cocaine seeking behavior. The mPFC also sends glutamatergic projections to the pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDT), which in turn send glutamatergic and cholinergic efferents to the ventral tegmental area (VTA) where they synapse on dopaminergic cells that innervate limbic structures including the nucleus accumbens. The goal of these experiments was to examine a potential role for the PPTg/LDT in the reinstatement of cocaine seeking. All rats were trained to self-administer cocaine (0.25 mg, i.v.) on a fixed-ratio 5 schedule of reinforcement. Cocaine self-administration behavior was extinguished and a series of subsequent pharmacological experiments were performed to assess the potential role of the mPFC, PPTg/LDT and VTA in the reinstatement of cocaine seeking. Administration of the D1-like dopamine receptor agonist SKF-81297 (1.0 [mu]g) directly into the mPFC produced a small, but statistically significant, increase in cocaine seeking behavior. Furthermore, microinjection of the ionotropic glutamate receptor antagonist CNQX (0.3 [mu]g) into the PPTg/LDT attenuated the reinstatement of drug seeking induced by a priming injection of cocaine (10 mg/kg, i.p.). Intra-VTA administration of CNQX, the nicotinic receptor antagonist mecamylamine (10.0 [mu]g) or the muscarinic receptor antagonist scopolamine (24.0 [mu]g) also blocked cocaine seeking. Taken together, these results suggest that cocaine priming-induced reinstatement of drug seeking is mediated in part by a serial polysynaptic limbic subcircuit encompassing the mPFC, PPTg/LDT and VTA. Author Affiliation: (1)Department of Psychiatry, University of Pennsylvania School of Medicine, 125 South 31st Street, Philadelphia, PA 19104, USA (2)Department of Pharmacology, Boston University School of Medicine, Boston, MA, USA Article History: Received 25 February 2009, revised 13 July 2009, accepted 17 July 2009 Article note: Dr H. D. Schmidt, as above., E-mail: hschmidt@mail.med.upenn.edu