Animal Models of the Binge/Intoxication Stage of the Addiction Cycle

Drug Taking in the Presence of Aversive Consequences

Drug taking or drug-seeking behavior that is impervious to environmental adversity or punishment captures elements of the compulsive nature of drug addiction associated with the binge/intoxicationstage of the addiction cycle. From the perspective of the DSM-IV, such drug seeking fits well with the criterion of continued substance use despite knowledge of having a persistent physical or psychological problem.

FIGURE 3.6 Changes in intracranial self-stimulation reward thresholds (Z-scores) in rats for various doses of heroin, morphine, nicotine, cocaine, D-amphetamine, and methamphetamine. A Z-score is based on the pre- and post-drug changes in threshold, and a Z-score of ± 2.0 indicates the 95% confidence limit based on the mean and standard deviation for all saline days. [Taken with permission from Hubner CB, Kornetsky C. Heroin, 6-acetylmorphine and morphine effects on threshold for rewarding and aversive brain stimulation. Journal of Pharmacology and Experimental Therapeutics, 1992, (260), 562–567 (heroin, morphine); Huston-Lyons D, Kornetsky C. Effects of nicotine on the threshold for rewarding brain stimulation in rats. Pharmacology Biochemistry and Behavior, 1992, (41), 755–759 (nicotine); Izenwasser S, Kornetsky C. Brain stimulation reward: a method for assessing the neurochemical bases of drug-induced euphoria. In: Watson RR (ed.) Drugs of Abuse and Neurobiology. CRC Press, Boca Raton FL, 1992, pp. 1–21 (cocaine); Kornetsky C. Brain stimulation reward: a model for the neuronal bases for drug-induced euphoria. In: Brown RM, Friedman DP, Nimit Y (eds.) Neuroscience Methods in Drug Abuse Research (series title: NIDA Research Monograph, vol. 62). National Institute on Drug Abuse, Rockville MD, 1985, pp. 30–50 (D-amphetamine); Sarkar M, Kornetsky C. Methamphetamine’s action on brain-stimulation reward threshold and stereotypy. Experimental and Clinical Psychopharmacology, 1995, (3), 112–117 (methamphetamine).]

FIGURE 3.7 The place conditioning procedure in the rat. Animals experience two distinct neutral environments (here, black and white shaded) paired spatially and temporally with distinct unconditioned stimuli (here, drug on days 2, 4, and 6 and saline on days 3, 5, and 7). On day 8, the rat is given the opportunity to enter either environment in a drug-free state, and the time spent in each environment is used as an index of the reinforcing value of each unconditioned stimulus. These time values are often compared with baseline preference for each environment (here, measured on day 1). [Taken with permission from Swerdlow NR, Gilbert D, Koob GF. Conditioned drug effects on spatial preference: critical evaluation. In: Boulton AA, Baker GB, Greenshaw AJ (eds.) Psychopharmacology (series title: Neuromethods, vol. 13). Humana Press, Clifton NJ, 1989, pp. 399–446.]

The presentation of an aversive stimulus, like a mild footshock, suppresses cocaine-seeking behavior in rats that have limited access (e.g., less than 3 h access to the drug per day). The aversive stimulus also suppresses sucrose seeking (a conventional reinforcer). This situation changes, however, when the animals are given extended access for, say, 6 h. The animals’ sucrose-seeking behavior continues to be suppressed by the aversive stimulus, but the rats’ cocaine-seeking behavior does not diminish when confronted with the same aversive conditioned stimulus. For example, dependent rats display more persistent alcohol consumption than nondependent rats as increasing amounts of the bitter-tasting, aversive substance quinine is added to the solution (that is, dependent rats continue to consume alcohol despite the aversive bitter taste of quinine). This is considered a measure of compulsive-like alcohol intake (Figure 3.8).

FIGURE 3.8 Compulsive-like drinking (i.e., persistent alcohol drinking despite the aversive bitter taste of quinine added to the alcohol solution) in dependent alcohol vapor-exposed rats during acute alcohol withdrawal. The data represent the percentage change from baseline (i.e., lever presses for alcohol alone before quinine adulteration). [Taken with permission from Vendruscolo LF, Barbier E, Schlosburg JE, Misra KK, Whitfield T Jr., Logrip ML, Rivier CL, Repunte-Canonigo V, Zorrilla EP, Sanna PP, Heilig M, Koob GF. Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats. Journal of Neuroscience, 2012, (32), 7563–7571.]

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