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Deletion of the GABA(A) α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking

RATIONALE: GABA(A) 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 sensi...

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Autores principales: Dixon, C. I., Halbout, B., King, S. L., Stephens, D. N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057633/
https://www.ncbi.nlm.nih.gov/pubmed/24481569
http://dx.doi.org/10.1007/s00213-014-3443-3
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author Dixon, C. I.
Halbout, B.
King, S. L.
Stephens, D. N.
author_facet Dixon, C. I.
Halbout, B.
King, S. L.
Stephens, D. N.
author_sort Dixon, C. I.
collection PubMed
description RATIONALE: GABA(A) 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 GABA(A) 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.
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spelling pubmed-40576332014-06-18 Deletion of the GABA(A) α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking Dixon, C. I. Halbout, B. King, S. L. Stephens, D. N. Psychopharmacology (Berl) Original Investigation RATIONALE: GABA(A) 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 GABA(A) 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. Springer Berlin Heidelberg 2014-01-31 2014 /pmc/articles/PMC4057633/ /pubmed/24481569 http://dx.doi.org/10.1007/s00213-014-3443-3 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/2.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Investigation
Dixon, C. I.
Halbout, B.
King, S. L.
Stephens, D. N.
Deletion of the GABA(A) α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking
title Deletion of the GABA(A) α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking
title_full Deletion of the GABA(A) α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking
title_fullStr Deletion of the GABA(A) α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking
title_full_unstemmed Deletion of the GABA(A) α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking
title_short Deletion of the GABA(A) α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking
title_sort deletion of the gaba(a) α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057633/
https://www.ncbi.nlm.nih.gov/pubmed/24481569
http://dx.doi.org/10.1007/s00213-014-3443-3
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