An investigation into the role of mesoaccumbal GABAA receptor α2 subunit in mediating cocaine-facilitated conditioned behaviours using the RNA interference system

Sindarto, Marsha Moniaga (2019) An investigation into the role of mesoaccumbal GABAA receptor α2 subunit in mediating cocaine-facilitated conditioned behaviours using the RNA interference system. Doctoral thesis (PhD), University of Sussex.

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Abstract

α2 subunit-containing GABAA receptors (α2-GABAARs) are abundantly expressed in the nucleus accumbens (NAc), a region thought to be important in mediating cocaine’s reinforcing properties. This thesis develops viral-based RNAi tools in efforts to investigate the functional role of mesoaccumbal α2-GABAARs in mediating cocaine’s ability to facilitate conditioned behaviours (i.e. behavioural sensitisation and conditioned reinforcement).
RNA interference (RNAi)-mediated knockdown of the α2 subunit expression in the NAc core neither affected appetitive Pavlovian learning nor instrumental learning maintained by the conditioned reinforcer, but blocked cocaine facilitation of conditioned reinforcement. This behavioural phenotype was also observed upon α2 knockdown specifically in NAc core dopamine D2 receptor (D2R)-containing neurons, whereas α2 knockdown in mesoaccumbal D1R-containing neurons reduced the level of discriminated approach during Pavlovian learning. Further, α2 knockdown in the NAc core or shell did not block cocaine-induced sensitisation as previously observed in the constitutive knockouts (Dixon et al., 2010), but the latter increased acute locomotor responses to cocaine.
Data presented within this thesis indicate that GABAergic signalling via α2-GABAARs within the NAc is involved in some of the motivation-enhancing properties of cocaine, most likely via interactions with the dopaminergic system.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Psychology > Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology > BF0199 Behaviourism. Neobehaviourism. Behavioural psychology
Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry > QD0433 Nucleic acids > QD0434 Ribonucleic acids
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0438 Psychiatry > RC0554 Psychiatric aspects of personality and behavior conditions > RC0564 Drug abuse. Substance abuse
Depositing User: Library Cataloguing
Date Deposited: 15 Feb 2019 13:02
Last Modified: 15 Feb 2019 13:02
URI: http://srodev.sussex.ac.uk/id/eprint/81902

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