Animal models of drug craving

Abstract

Drug craving, the desire to experience the effect(s) of a previously experienced psychoactive substance, has been hypothesized to contribute significantly to continued drug use and relapse after a period of abstinence in humans. In more theoretical terms, drug craving can be conceptualized within the framework of incentive motivational theories of behavior and be defined as the incentive motivation to self-administer a psychoactive substance. The incentive-motivational value of drugs is hypothesized to be determined by a continuous interaction between the hedonic rewarding properties of drugs (incentive) and the motivational state of the organism (organismic state). In drug-dependent individuals, the incentive-motivational value of drugs (i.e., drug craving) is greater compared to non-drug-dependent individuals due to the motivational state (i.e., withdrawal) developed with repeated drug administration. In this conceptual framework, animal models of drug craving would reflect two aspects of the incentive motivation to self-administer a psychoactive substance. One aspect would be the unconditioned incentive (reinforcing) value of the drug itself. The other aspect would be relatively independent of the direct (unconditioned) incentive value of the drug itself and could be reflected in the ability of previously neutral stimuli to acquire conditioned incentive properties that could elicit drug-seeking and drug-taking behavior. Animal models of drug craving that permit the investigation of the behavioral and neurobiological components of these two aspects of drug craving are reviewed and evaluated. The models reviewed are the progressive ratio, choice, extinction, conditioned reinforcement and second-order schedule paradigms. These animal models are evaluated according to two criteria that are established herein as necessary and sufficient criteria for the evaluation of animal models of human psychopathology: reliability and predictive validity. The development of animal models of drug craving will have heuristic value and allow a systematic investigation of the neurobiological mechanisms of craving.

Constitutively Active Mu Opioid Receptors Mediate the Enhanced Conditioned Aversive Effect of Naloxone in Morphine-Dependent Mice

“…It has been hypothesized that this increase in constitutively active receptors following morphine administration plays a role in morphine dependence (Cruz et al, 1996;Wang et al, 1994). However, it is increasingly apparent that psychological as well as physical syndromes associated with opiate abstinence play a significant role in relapse to chronic drug intake (Markou et al, 1993;Schulteis and Koob, 1996). The conditioned aversive effect of antagonist-precipitated opiate withdrawal in animal models is considered reflective of this negative affective state (Azar et al, 2003).…”

Effects of hippocampal damage on reward threshold and response rate during self-stimulation of the ventral tegmental area in the rat

“…A second possibility relates to the hypothetical properties of inverted, U-shaped response functions that have been generated in self-stimulation [64] and self-administration experiments [26,35,36,62]. Thus, at low current intensities on the ascending limb of the curve, responding probably reflects the rewarding properties of the stimulation, in that higher currents elicit increasing rates of responding.…”

“…Addi-tionally, when sucrose pellets were substituted for the grain-based pellets, breakpoints of lesioned rats were differentially increased as compared to controls. As progressive ratio breakpoints are believed to reflect the amount of effort an animal will exert to obtain a reinforcer [22,23,35,53], these results were interpreted as indicating that the lesion had enhanced the incentive motivational properties of the delivered food pellets. Given the well known involvement of the NACC in rewarded behavior (see Ref.…”

Nicotine-Associated Cues Maintain Nicotine-Seeking Behavior in Rats Several Weeks after Nicotine Withdrawal: Reversal by the Cannabinoid (CB1) Receptor Antagonist, Rimonabant (SR141716)

“…Factors such as drug-associated environmental stimuli, stress, or drug priming can trigger craving in humans and drug-seeking behavior in laboratory animals (Shaham et al, 2003;Sinha et al, 2000;Weiss et al, 2001;Brody et al, 2002). Cue-induced drug-seeking behavior can be measured in animals using second-order schedules of drug reinforcement or extinction/reinstatement models (Markou et al, 1993). In the former, operant responding is maintained not only by the drug but also by drug-associated stimuli that serve as conditioned reinforcers Schindler et al, 2002).…”