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Environmental condition alters amphetamine self-administration: role of the MGluR5 receptor and schedule of reinforcement

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Abstract

Rationale

Evidence suggests that differential rearing influences the function of a receptor subtype critical for maintaining glutamate homeostasis. Maintaining homeostatic glutamatergic function may be an important protector against drug abuse.

Objective

This study sought to determine if differential rearing influences the function of a receptor critical for glutamate homeostasis, which could in turn affect rates of amphetamine self-administration.

Methods

Rats were assigned to enriched (EC), isolated (IC), or standard (SC) conditions. After rearing for 30 days, rats were trained to lever press for sucrose reinforcement before the implantation of indwelling jugular catheters. After reaching stable responding for amphetamine (0.03 or 0.1 mg/kg/infusion), rats were injected with five doses (0, 0.3, 1.0, 3.0, and 5.0 mg/kg) of the mGluR5 antagonist, 3-((2-methyl-1,3-thiazol-4-yl)ethynyl) pyridine hydrochloride (MTEP), 30 min before self-administration sessions. Following fixed-ratio (FR-1) testing, rats were administered identical doses of MTEP on a progressive-ratio (PR) reinforcement schedule.

Results

MTEP (3.0 mg/kg) attenuated FR-1 self-administration (0.03 mg/kg/infusion) in IC rats. MTEP also dose-dependently attenuated amphetamine self-administration (0.1 mg/kg/infusion) during FR-1 and PR sessions, with 5.0 mg/kg MTEP attenuating amphetamine self-administration in IC and SC rats and 3.0 mg/kg MTEP attenuating amphetamine self-administration in EC and SC rats. PR results also revealed that IC rats not treated with MTEP were more motivated to self-administer the higher dose of amphetamine.

Conclusions

These results suggest that the mGlu5 receptor mediates differences in drug-taking behavior among differentially reared rats. Isolation also decreased sensitivity to MTEP, suggesting that environmental factors alter glutamate homeostasis which subsequently affects sensitivity and motivation to self-administer amphetamine.

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Acknowledgments

Research reported in this article was supported by NIH through NIDA grant #: R15DA035435, and Kansas State University. We thank Michele Ulmer, Greg Erickson, Lauren Komer, Emily Reinhardt, Christy Peterson, and Alexander Howard for their assistance in daily experimental procedures, as well as Erik Garcia for providing surgical assistance.

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Authors and Affiliations

  1. Department of Psychological Sciences, Kansas State University, 492 Bluemont Hall, Manhattan, KS, 66506, USA

    D. L. Arndt, K. C. Johns, Z. K Dietz & M. E. Cain

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  1. D. L. Arndt
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  2. K. C. Johns
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  3. Z. K Dietz
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Correspondence to D. L. Arndt.

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Arndt, D.L., Johns, K.C., Dietz, Z.K. et al. Environmental condition alters amphetamine self-administration: role of the MGluR5 receptor and schedule of reinforcement. Psychopharmacology 232, 3741–3752 (2015). https://doi.org/10.1007/s00213-015-4031-x

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  • DOI: https://doi.org/10.1007/s00213-015-4031-x

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