Chunk #33 — 2. Neural substrates for the negative emotional state associated with addiction — 2.3. Neuropharmacological studies of the aversive stimulus effects of drug withdrawal
Acute opioid dependence has been defined as the precipitation of withdrawal-like signs by opioid antagonists following a single dose or short-term administration of an opioid agonist (Martin and Eades, 1964). Rats show a reliable conditioned place aversion precipitated by a low dose of naloxone after a single morphine injection that reflects a motivational component of acute withdrawal (Azar et al., 2003). Acute opioid withdrawal also produces increases in reward thresholds (Liu and Schulteis, 2004), suppression in operant responding (Schulteis et al., 2003) and increased anxiety-like behavior in the elevated plus maze (Zhang and Schulteis, 2008). Using the conditioned place aversion paradigm, the opioid partial agonist buprenorphine dose-dependently decreased the place aversion produced by precipitated opioid withdrawal. Systemic administration of a CRF1 receptor antagonist and direct intracerebral administration of a peptide CRF1/CRF2 antagonist also decreased opioid withdrawal-induced place aversions (Stinus et al., 2005; Heinrichs et al., 1995). Functional noradrenergic antagonists blocked opioid withdrawal-induced place aversion (Delfs et al., 2000).
