Fig. 7.

A hypothetical representation of opiate motivation in the non-deprived and drug-dependent and withdrawn motivational states. In non-deprived animals (left), activation of VTA GABA_A receptors produces hyperpolarization (inhibition). Opiate binding to presynaptic µ-opioid receptors reduces GABA_A receptor activation. Consequently, VTA GABA cells are depolarized as a result of the loss of an inhibitory input. In turn, VTA dopamine cells remain inhibited, and an opiate reinforcement signal is sent to the TPP. Conversely, in opiate-deprived animals (right), activation of VTA GABA_A receptors produces depolarization (excitation). Opiate binding to presynaptic µ-opioid receptors again reduces VTA GABA_A receptor activation. In turn, VTA GABA cells are hyperpolarized due to the loss of an excitatory input, and VTA dopamine cells are disinhibited, leading to the production of a dopamine-dependent opiate motivational signal initiated in the VTA and terminating in the NAc. The change to a drug-deprived state can be accomplished by extensive opiate exposure (enough to produce withdrawal), intra-VTA furosemide administration, or food deprivation, and can be prevented by intra-VTA acetazolamide administration