Brief ReportPositive Allosteric Modulation of mGluR5 Receptors Facilitates Extinction of a Cocaine Contextual Memory
Section snippets
Animals
All procedures were conducted with the approval of an Institutional Animal Care and Use Committee. Male Sprague-Dawley rats (200–275 g, Harlan, Indianapolis, Indiana) were maintained on a 12 hour light-dark cycle (lights off at 7:00 am), and all experimentation was conducted during the dark phase. Rats were given ad libitum access to food and water throughout all procedures except during behavioral testing.
Apparatus
The CPP apparatus (Med Associates, St. Albans, Vermont) consisted of two adjacent
Results
Conditioning with cocaine (10 mg/kg) produced a significant place preference in all groups, as evidenced by a significant increase in the percent time spent in the initial nonpreferred side (Figures 1A and 1C). Cocaine CPP was observed to extinguished during the extinction test sessions as follows: vehicle (E5), .3 mg/kg CDPPB (E4), 3 mg/kg CDPPB (E1), 30 mg/kg CDPPB (E2), 30 mg/kg CDPPB + 1 mg/kg MTEP (E5), 30 mg/kg CDPPB + .1 mg/kg MK-801 (CPP was not extinguished after 5 days of extinction
Discussion
We found that the systemically active mGluR5 positive allosteric modulator CDPPB dose-dependently facilitated the extinction of a cocaine contextual memory, as evidenced by fewer extinction test sessions required to reach extinction criteria. This effect appeared to be mediated by both mGluR5 and NMDA receptors, because the effect of the highest dose of CDPPB tested was reversed by coadministration of MTEP and MK-801, respectively. CDPPB did not influence locomotor activity, nor did it exhibit
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