Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767070
Title: An investigation into the role of mesoaccumbal GABAA receptor α2 subunit in mediating cocaine-facilitated conditioned behaviours using the RNA interference system
Author: Sindarto, Marsha Moniaga
ISNI:       0000 0004 7657 668X
Awarding Body: University of Sussex
Current Institution: University of Sussex
Date of Award: 2019
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.767070  DOI: Not available
Keywords: BF0199 Behaviourism. Neobehaviourism. Behavioural psychology ; QD0434 Ribonucleic acids ; RC0564 Drug abuse. Substance abuse
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