A crucial question in drug addiction research concerns whether the varying reports of dopamine-independent and dopamine-dependent motivation can be integrated. According to one theory, the prior drug history of a subject — that is to say, whether they have received minimal or chronic drug exposure — determines whether opiate motivation is dependent upon the brainstem tegmental pedunculopontine nucleus (TPP) or dopamine neurotransmission. The biological analogue of this change is thought to be a switch in the signalling properties (from hyperpolarizing to depolarizing) of ventral tegmental area (VTA) gamma-aminobutyric acid subtype-A (GABAA) receptors. In this thesis, I demonstrate that the mechanisms underlying opiate motivation can be selected artificially by manipulating the signalling properties of VTA GABAA receptors, irrespective of the past drug history of the subject. Furthermore, I suggest that these same VTA GABAA receptors also play a similar role in controlling ethanol motivation. Indeed, the mechanisms underlying ethanol motivation can be doubly dissociated in a manner similar to that observed with opiates. However, whereas opiate motivation is TPP-dependent in the drug-naive state, I found that ethanol motivation was dependent on dopamine neurotransmission (via the D2 receptor) in drug-naive animals. Conversely, ethanol motivation was TPP-dependent in ethanol-deprived mice (as opposed to opiate motivation being dopamine-dependent in opiate-deprived animals). These effects are consistent with a VTA GABAA receptor switching mechanism identical to the one seen in the case of opiate motivation.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/32827 |
| Date | 31 August 2012 |
| Creators | Ting-A-Kee, Ryan Anthony |
| Contributors | van der Kooy, Derek |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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