Peripheral versus intracerebroventricular administration of quaternary naltrexone and the enhancement of Pavlovian conditioning.

When rats are placed in a context with mild electric shock (1 mA/0.75 s), the environmental cues alone can provoke an immobile crouching behavior termed freezing. Freezing response is a Pavlovian conditional response provoked by stimuli that come to be associated with shock. Previous research has shown that peripheral injection of opioid antagonists can enhance this response. Two experiments were conducted to determine if peripheral and/or central opioid mechanisms are involved in this enhancement of freezing by employing quaternary naltrexone (QNTX), an opioid antagonist which does not readily penetrate the 'blood-brain barrier'. QNTX (5 and 10 micrograms/rat) administered i.c.v. prior to shock significantly enhanced freezing 24 h later, whereas i.p. injected QNTX, at doses as high as 20 mg/kg, had no effect. These results suggest that the enhancement of conditional freezing produced by QNTX is mediated by central, not peripheral, opioid mechanisms.