Chunk #31 — 2. Neural substrates for the negative emotional state associated with addiction — 2.3. Neuropharmacological studies of the aversive stimulus effects of drug withdrawal
Place aversion has been used to measure the aversive stimulus effects of withdrawal, mostly in the context of opioids (Hand et al., 1988; Stinus et al., 1990). In contrast to conditioned place preference, rats exposed to a particular environment while undergoing precipitated withdrawal to opioids spend less time in the withdrawal-paired environment when subsequently presented with a choice between that environment and an unpaired environment. These aversive stimulus effects can be measured from 24 h to 16 weeks later (Hand et al., 1988; Stinus et al., 1990, 2000). The place aversion does not require maintenance of opioid dependence for its manifestation. Such an association continues to be manifested weeks after animals are “detoxified” (e.g., after the morphine pellets are removed) (see Baldwin and Koob, 1993; Stinus et al., 2000). In addition, a place aversion in opioid-dependent rats can be observed with doses of naloxone below which somatic signs of withdrawal are observed (Schulteis et al., 1994). Although naloxone itself will produce a place aversion in nondependent rats, the threshold dose required to produce a place aversion decreases significantly in dependent
