Deletion of the GABAA α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking

Psychopharmacology (Berl). 2014 Jul;231(13):2695-703. doi: 10.1007/s00213-014-3443-3. Epub 2014 Jan 31.

Abstract

Rationale: GABAA receptors containing α2-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 α2-subunit results in an absence of sensitisation to cocaine.

Objective: We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure.

Methods: α2-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 α2-subunit may be involved in modulating the "energising" aspect of cocaine's effects on reward-seeking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Cues
  • Dose-Response Relationship, Drug
  • Drug-Seeking Behavior*
  • Genotype
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, GABA-A / genetics*
  • Reinforcement, Psychology
  • Reward*
  • Self Administration

Substances

  • Gabra2 protein, mouse
  • Receptors, GABA-A
  • Cocaine