Animal Models of the Preoccupation/Anticipation Stage of the Addiction Cycle

Context-Induced Reinstatement

Drug-associated stimuli that signal the response-contingent availability of intravenous drug also reliably elicit drug seeking behavior in experimental animals, and responding for these stimuli is highly resistant to extinction (See et al., 1999). Subsequent re-exposure to the drug discriminative stimulus after extinction but not re-exposure to a nonreward discriminative stimulus produces strong recovery of responding at the previously active lever in the absence of any further drug availability. Cues associated with the availability of oral alcohol self-administration can also reinstate responding in the absence of the primary reinforcer (Katner et al., 1999; Ciccocippo et al., 2001; Crombag et al., 2002, 2008).


Animal Models of the Preoccupation/Anticipation Stage of the Addiction Cycle

  • Resistance to extinction associated with drug self-administration
  • Drug-induced reinstatement
  • Cue-induced reinstatement
  • Context-induced reinstatement (“renewal”)
  • Cue-induced reinstatement without extinction (“relapse”)
  • Stress-induced reinstatement
  • Second-order schedules of reinforcement
  • Protracted abstinence
  • Conditioned withdrawal

FIGURE 3.12 Mean number of responses in rats per 10 min during self-administration (continuous reinforcement, CR), during extinction, and after cocaine priming injections of 2.0, 1.0, and 0.5 mg/kg or after a “dummy trial” (0.0 mg/kg). “P” indicates the point at which the priming injection was given. The mean values during extinction are based on eight determinations for each of five rats; the means after the priming infusions are based on two determinations per rat for each of five rats. Closed circles, 0.0 mg/kg; open circles, 0.5 mg/kg; triangles, 1.0 mg/kg; squares, 2.0 mg/kg. [Taken with permission from de Wit H, Stewart J. Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology, 1981, (75), 134–143.]

FIGURE 3.13Lever-press responses at an active (A) and inactive (B) lever in rats during self-administration training, extinction, and reinstatement sessions. Training Phase: Cocaine-reinforced (●) and saline/nonreinforced (◯) responses during the final 3 days of the self-administration phase in rats trained to associate discriminative stimuli with the availability of intravenous cocaine (S+) or saline (S−). Rats were designated for tests of resistance to the extinction of cocaine-seeking behavior induced by the cocaine S+ during the Reinstatement Phase. Extinction Phase: Extinction responses at criterion (< 4 responses/session over three consecutive days). The number of days required to reach the criterion was 15.3 ± 3.9. Reinstatement Phase: Responses in the presence of the S+ and S−. Exposure to the S+ elicited significant recovery of responding in the absence of further drug availability, whereas responding in the presence of the S− remained at extinction levels. [Taken with permission from Weiss F, Martin-Fardon R, Ciccocioppo R, Kerr TM, Smith DL, Ben-Shahar O. Enduring resistance to extinction of cocaine-seeking behavior induced by drug-related cues. Neuropsychopharmacology, 2001, (25), 361–372.]

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