Chunk #35 — 2. Neural substrates for the negative emotional state associated with addiction — 2.4. Neuropharmacological studies of the anxiety-like effects of drug withdrawal
Another common response to acute withdrawal and protracted abstinence from all major drugs of abuse is the manifestation of anxiety-like responses. Animal models have revealed anxiety-like response to all major drugs of abuse during acute withdrawal. The dependent variable is often a passive response to a novel and/or aversive stimulus, such as the open field or elevated plus maze, or an active response to an aversive stimulus, such as defensive burying of an electrified metal probe. Withdrawal from repeated administration of cocaine produces an anxiogenic-like response in the elevated plus maze and defensive burying test, both of which are reversed by administration of CRF antagonists (Sarnyai et al., 1995; Basso et al., 1999). Precipitated withdrawal in opioid dependence also produces anxiety-like effects (Schulteis et al., 1998; Harris and Aston-Jones, 1993). Ethanol withdrawal produces anxiety-like behavior that is reversed by intracerebroventricular administration of CRF1/CRF2 peptidergic antagonists (Baldwin et al., 1991), small molecule CRF1 antagonist (Knapp et al., 2004; Overstreet et al., 2004; Funk et al., 2007), and intracerebral administration of a peptidergic CRF1/CRF2 antagonist into the amygdala (Rassnick et al., 1993).
