GABAA receptors signal bidirectional reward transmission from the ventral tegmental area to the tegmental pedunculopontine nucleus as a function of opiate state

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Abstract
The brainstem tegmental pedunculopontine nucleus (TPP) is involved in reward signalling and is functionally and anatomically linked to the VTA. We examined the possible role of the TPP as a reward transmission output for GABAA receptors in the VTA in rats not previously exposed to opiates vs. rats that were chronically exposed to and in withdrawal from opiates or in rats that had recovered from chronic opiate exposure. Bilateral lesions of the TPP blocked the rewarding effects of a GABAA antagonist but not the rewarding effects of a GABAA receptor agonist in rats previously unexposed to opiates. This functional pattern was reversed in rats that were dependent on opiates and in withdrawal. However, once rats had recovered from chronic opiate exposure the functional parameters of VTA GABAA receptor reward signalling reverted to the pattern observed in animals that had not been exposed to opiates. These findings suggest that GABAA receptors in the VTA can regulate differential reward signalling through separate neural systems during the transition from a drug-naive to a drug-dependent and withdrawn state.

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