Archival ReportBehavioral and Functional Evidence of Metabotropic Glutamate Receptor 2/3 and Metabotropic Glutamate Receptor 5 Dysregulation in Cocaine-Escalated Rats: Factor in the Transition to Dependence
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Animals
Male Wistar rats (200 – 250 g, Charles River, Wilmington, Massachusetts) were maintained on a 12-hour/12-hour light/dark cycle (lights off at 18:00). Food and water were available ad libitum. All procedures were conducted in strict adherence to the National Institutes of Health Guide for the Care and Use of Laboratory Animals (23) and were approved by the Institutional Animal Care and Use Committee of The Scripps Research Institute.
Cocaine Self-Administration Training
Rats (n = 55) were surgically prepared with indwelling silastic
Escalation of Cocaine Self-Administration
Cocaine self-administration progressively increased in the LgA group. Escalation of cocaine intake was observed beginning with session 7 in terms of responding over the entire 6-hour session [p < .01 vs. session 1 following one-way ANOVA, F(21,546) = 8.43, p < .001; Figure 1A, left panel] and session 5 in terms of first-hour responding [p < .01 vs. session 1 following one-way ANOVA, F(21,546) = 7.40, p < .001; Figure 1A, right panel] until session 22. In contrast, cocaine self-administration in
Discussion
In the present study, two agents known to dampen excitatory glutamatergic transmission by activating presynaptic and perisynaptic autoregulatory mGluR2/3 (LY379268) or by antagonizing excitatory postsynaptic mGluR5 (MTEP) attenuated the reinforcing effects of cocaine on a PR schedule. In rats showing escalated cocaine intake, the ability of the mGluR2/3 agonist LY379268 to diminish cocaine-maintained PR performance increased, whereas the effect of the mGluR5 antagonist MTEP was blunted. This
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2021, Pharmacology and TherapeuticsCitation Excerpt :Moreover, Knackstedt et al. (2014) showed that the NAc core mGluR5 modulates drug-seeking following both extinction and abstinence from cocaine self-administration. There is also some preclinical evidence that mGlu5 receptors are involved in shifting from recreational drug-taking to cocaine use disorder (Hao et al., 2010). However, according to us, further studies, including punishment procedure, should be conducted to support this conclusion.