Endogenous opiate reward induced by an enkephalinase inhibitor, thiorphan, injected into the ventral midbrain

Opiates are known to be reinforcing when injected into the ventral tegmental area (VTA). The present study produced conditioned reinforcement with local injections of exogenous d-ala²-met⁵-enkephalinamide (DALA), a potent analogue of met-enkephalin, and with thiorphan, an enkephalinase inhibitor which protects endogenous opiates from enzymic degradation. In a conditioned place preference paradigm, rats received injections of DALA (1.0, 3.0, or 8.0 μg), thiorphan (60 μg), and/or naloxone (10 μg), or saline vehicle. Conditioned reinforcement was obtained with 8.0 μg of DALA and also with thiorphan but not with thiorphan plus naloxone. This suggests that reward can be generated by endogenous opiates in the VTA. Tests during the light phase and dark phase suggested that diurnal periodicity may play a role in opiate reward. It is concluded that the VTA can generate conditioned reward through transmitter-receptor interaction involving an endogenous opiate substrate which is probably enkephalinergic.