Opioid receptors regulate the extinction of Pavlovian fear conditioning

Rats received a single pairing of an auditory conditioned stimulus (CS) with a footshock unconditioned stimulus (US). The fear (freezing) that had accrued to the CS was then extinguished. Injection of naloxone prior to this extinction significantly impaired the development of extinction. This impairment was mediated by opioid receptors in the brain and was not observed when naloxone was injected after extinction training. Finally, an injection of naloxone on test failed to reinstate extinguished responding that had already accrued to the CS. These experiments show that opioid receptors regulate the devel-opment, but not the expression, of fear extinction and are discussed with reference to the roles of opioid receptors in US processing, memory, and appetitive motivation. Activity at opioid receptors modulates the acquisition of Pav-lovian aversive conditioning. Systemic or intracerebral adminis-trations of opioid receptor agonists typically impair, whereas such administrations of opioid receptor antagonists facilitate, acquisi-tion of aversive conditioning across a variety of species (e.g., rat, rabbit, mouse) and conditioning preparations (e.g., freezing, heart rate, eyeblink; for a review, see Fanselow, 1998). Opioid peptide