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Deletion of the GABAA a2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

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posted on 2023-06-15, 14:44 authored by Claire Dixon, B Halbout, Sarah KingSarah King, D N Stephens
Rationale GABAA receptors containing a2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the a2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA a2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods a2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the a2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking.

Funding

Molecular and physiological mechanism of GABA(A) receptor function in striatal circuits underlying addiction; R3AD; MRC-MEDICAL RESEARCH COUNCIL; G0802715 90054

Involvement of alpha2 subunit-containing GABAA receptors in neural circuits underlying drug abuse.; R31T; MRC-MEDICAL RESEARCH COUNCIL; GO600874-79039

GABA alpha Receptors in accumbens neural circuits underlying drug abuse: a target for treatm; G0211; MRC-MEDICAL RESEARCH COUNCIL; G1000008-94406

History

Publication status

  • Published

File Version

  • Published version

Journal

Psychopharmacology

ISSN

0033-3158

Publisher

Springer

Issue

13

Volume

231

Page range

2695-2703

Department affiliated with

  • Psychology Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2014-07-02

First Open Access (FOA) Date

2014-07-15

First Compliant Deposit (FCD) Date

2014-07-02

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