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

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.

Histone deacetylase inhibition differentially attenuates cue-induced reinstatement: An interaction of environment and acH3K9 expression in the dorsal striatum.

“…Across 10 sessions, acquisition of amphetamine (0.1 mg/kg/ infusion) self-administration was not affected by either environmental condition, F(2, 36) ϭ 1.00, p ϭ .378, 2 ϭ .05 or HDAC inhibition, F(1, 36) ϭ 0.55, p ϭ .464, 2 ϭ .02, data not shown. Consistent with previous research (Arndt et al, 2015;Bardo et al, 2001), differential rearing did not alter self-administration of a high dose of amphetamine and therefore it is not surprising that TsA did not differentially alter responding.…”

Alternation in dopamine D2-like and metabotropic glutamate type 5 receptor density caused by differing housing conditions during abstinence from cocaine self-administration in rats

“…Our study is the first to show changes in the mGlu 5 receptor density and affinity due to housing conditions following exposure to cocaine. So far, limited research has been conducted to study the EE and IC on mGlu 5 receptors, and our findings show that both of the above-mentioned conditions alter the function of receptors critical for maintaining glutamate homeostasis, which can lead to altered drug-taking behaviours (Arndt et al, 2015).…”

Differential housing and novelty response: Protection and risk from locomotor sensitization

“…The current experiment did not examine if a similar relationship exists between housing condition and novelty during psychostimulant self-administration. An extensive literature indicates that the novelty response predicts the acquisition of low unit doses of psychostimulants (Piazza et al, 1989; Piazza et al, 1990), and that enrichment decreases the self-administration of low unit doses of amphetamine (Arndt et al, 2015; Bardo et al, 2001). Therefore, we hypothesize that a similar mediation pattern between novelty and housing conditions would remain during self-administration of low unit doses.…”

“…Our EC, IC, and SC environmental conditions have been explained previously articles (Arndt et al, 2014; Arndt et al, 2015; Cain et al, 2012; Gill et al, 2012) Briefly, rats in the EC were housed in a large metal cage (60×120×45 cm) that was lined with paper pulp bedding. The EC cage contained 8–12 other rats and contained 14 objects (toys, PVC pipe).…”