Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Mar;226(1):167-76.
doi: 10.1007/s00213-012-2897-4. Epub 2012 Oct 27.

Cocaine-related Behaviors in Mice With Deficient Gliotransmission

Affiliations
Free PMC article

Cocaine-related Behaviors in Mice With Deficient Gliotransmission

Jill R Turner et al. Psychopharmacology (Berl). .
Free PMC article

Abstract

Rationale: Astrocytes play an integral role in modulating synaptic transmission and plasticity, both key mechanisms underlying addiction. However, while astrocytes are capable of releasing chemical transmitters that can modulate neuronal function, the role of these gliotransmitters in mediating behaviors associated with drugs of abuse has been largely unexplored.

Objectives: The objective of the present study was to utilize mice with astrocytes that lack the ability to release chemical transmitters to evaluate the behavioral consequence of impaired gliotransmission on cocaine-related behaviors. These mice have previously been used to examine the role of gliotransmission in sleep homeostasis; however, no studies to date have utilized them in the study of addictive behaviors.

Methods: Mice expressing a dominant-negative SNARE protein selectively in astrocytes (dnSNARE mice) were tested in a variety of behavioral paradigms examining cocaine-induced behavioral plasticity. These paradigms include locomotor sensitization, conditioned place preference followed by cocaine-induced reinstatement of CPP, and cocaine self-administration followed by cue-induced reinstatement of cocaine-seeking behavior.

Results: Wild-type and dnSNARE mice demonstrated no significant differences in the development or maintenance of locomotor sensitization. While there were non-significant trends for reduced CPP following a low dose of cocaine, drug-induced reinstatement of CPP is completely blocked in dnSNARE mice. Similarly, while dnSNARE mice demonstrated a non-significant trend toward reduced cocaine self-administration compared with wild-type mice, dnSNARE mice do not demonstrate cue-induced reinstatement in this paradigm.

Conclusions: Gliotransmission is necessary for reinstatement of drug-seeking behaviors by cocaine or associated cues.

Figures

Figure 1
Figure 1. Development and expression of locomotor sensitization in dnSNARE mice
Cocaine locomotor sensitization to 5mg/kg (A), 10 mg/kg (B), and 20 mg/kg (C) cocaine in wildtype (closed symbols) and dnSNARE (open symbols) mice. Cocaine wildtype mice significant relative to wildtype saline control: *, p<0.05; **, p<0.01; ***, p<0.001. Cocaine dnSNARE significant relative to dnSNARE saline control: &, p<0.05; &&&, p<0.001. Significant effects of previous drug treatment regardless of genotype on challenge day: ^, p<0.05; ^^^, p<0.001. Number of subjects in each treatment: 5mg/kg, n=6–8; 10mg/kg, n=7–8; 20mg/kg, n=6–7.
Figure 2
Figure 2. Development of conditioned place preference in dnSNARE mice
(A) Side preferences of wildtype and dnSNARE mice in the CPP chamber. (B) Conditioned place preference scores for cocaine-treated wildtype (solid bars) and dnSNARE (striped bars) mice at the 5mg/kg, 10mg/kg, and 20mg/kg doses. Significant effect of day: ^^^, p<0.001. Number of wildtype and dnSNARE mice in each treatment: 5mg/kg, n=9–10; 10mg/kg, n=8; 20mg/kg, n=12.
Figure 3
Figure 3. Reinstatement of conditioned place preference in dnSNARE mice
(A) Experimental paradigm for conditioned place preference and reinstatement. PRE: Preconditioning day 1. Day 2–9: S- saline, C- cocaine (10 mg/kg, i.p.). TEST: Test on day 10 to confirm CPP. Day 11–24: saline injections in conditioning boxes to extinguish behavior. TEST: Test on day 25 to confirm CPP is extinguished. REINSTATEMENT: Reinstatement of CPP on day 26 via an acute i.p. injection of 10mg/kg cocaine. (B) Conditioned place preference scores of wildtype and dnSNARE mutant mice following cocaine (10 mg/kg) conditioning, extinction, and reinstatement. Cocaine wildtype mice significant relative to wildtype saline control on same testing day: *, p<0.05. Cocaine dnSNARE significant relative to dnSNARE saline control on same testing day: &, p<0.05. Wildtype cocaine group significantly different from dnSNARE cocaine group: ##, p<0.01. Number of subjects in each treatment: n=8.
Figure 4
Figure 4. dnSNARE mice exhibit decreased cocaine self-administration at low doses and decreased cue-induced reinstatement of cocaine seeking
Food self-administration (A) and cocaine self-administration (B) behavior in wildtype (open symbols) and dnSNARE (closed symbols) mice. (C) Cocaine self-administration dose response in wildtype (open symbols) and dnSNARE (closed symbols) mice. (D) Active responses following extinction and cue-induced reinstatement in wildtype and dnSNARE mice. dnSNARE group significantly different from wildtype control on RI test day: ###, p<0.001. Number of wildtype and dnSNARE mice at each self-administration stage: (A, food self-administration) wildtype, n=9, dnSNARE, n=12; (B, cocaine self-administration) wildtype, n=5, dnSNARE, n=10; (C, cocaine dose-response) wildtype, n=5, dnSNARE, n=9; (D, cue-induced reinstatement) wildtype, n=4, dnSNARE, n=9.

Similar articles

See all similar articles

Cited by 24 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback