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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:767070 |
| Date | January 2019 |
| Creators | Sindarto, Marsha Moniaga |
| Publisher | University of Sussex |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://sro.sussex.ac.uk/id/eprint/81902/ |
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