Ventral Tegmental Area GABAA Receptors Mediate the Change from a Drug-Naive to an Opiate- or Ethanol-Deprived Motivational State

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.