Deletion of the GABAA α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking.
BACKGROUND
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.
School of Psychology, University of Sussex, Falmer, Brighton, BN1 9QG, UK.
C I
CI
Dixon
B
B
Halbout
S L
SL
King
D N
DN
Stephens
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011963:Receptors, GABA-A / Q000235:genetics*; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration
C493920:Gabra2 protein, mouse; D011963:Receptors, GABA-A; D003042:Cocaine