Effects of mGluR1 antagonism in the dorsal hippocampus on drug context-induced reinstatement of cocaine-seeking behavior in rats.
BACKGROUND
The functional integrity of the dorsal hippocampus (DH) is necessary for drug context-induced reinstatement of cocaine seeking. However, the neuropharmacological mechanisms of this phenomenon are poorly understood.


OBJECTIVE
Given the known significance of group I metabotropic glutamate receptors (mGluRs), including the mGluR1 subtype, in drug-induced behaviors, the present study was designed to evaluate the contribution of mGluR1s in the DH to drug context-induced reinstatement of extinguished cocaine-seeking behavior.


METHODS
Sprague-Dawley rats were trained to lever press for unsignaled cocaine infusions in a distinct environmental context (cocaine-paired context) followed by extinction training in a distinctly different environmental context (extinction context). Using a counterbalanced partial within-subjects testing design, rats were re-exposed to the cocaine-paired context or the extinction context while cocaine-seeking behavior (nonreinforced active lever pressing) was assessed. Prior to each test session, rats received bilateral microinfusions of the highly potent mGluR1-selective antagonist JNJ16259685 (0.6, 30, or 120 pg/0.5 microl per hemisphere) or vehicle into the DH or the overlying somatosensory cortex trunk region (SStr; anatomical control).


RESULTS
Intra-DH, but not intra-SStr, JNJ16259685 infusions dose dependently attenuated drug context-induced reinstatement of cocaine seeking relative to vehicle treatment, without attenuating instrumental behavior in the extinction context, general motor activity, or food-reinforced instrumental behavior in control experiments.


CONCLUSIONS
Stimulation of mGluR1s in the DH is necessary for incentive motivational and/or memory processes that contribute to drug context-induced cocaine-seeking behavior. These findings indicate that the mGluR1 is an interesting target from an addiction treatment perspective.
Xie
Xiaohu
X
Department of Psychology, University of North Carolina, CB# 3270, Davie Hall, Chapel Hill, NC, USA.
Ramirez
Donna R
DR
Lasseter
Heather C
HC
Fuchs
Rita A
RA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012055:Reinforcement Schedule; D012646:Self Administration
C495417:(3,4-dihydro-2H-pyrano(2,3)b-quinolin-7-yl)-(cis-4-methoxycyclohexyl) methanone; D011804:Quinolines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D003042:Cocaine