Cocaine-induced suppression of saccharin intake: A model of drug-induced devaluation of natural rewards.

Abstract

In Experiment 1, water-deprived Sprague-Dawley rats were given 5 min access to saccharin. This tube retracted, an empty tube advanced, and the rats were given 1 hr to lick the empty tube on a fixed-ratio 10 lick contingency to self-administer saline or cocaine (0.33 mg/infusion) via an intravenous catheter. The results showed that rats avoided intake of saccharin after saccharin-cocaine pairings and that greater avoidance of the gustatory cue was associated with greater cocaine self-administration. In Experiment 2, a similar dose-response function was obtained with either the empty tube or a lever as the operant. In Experiment 3, avoidance of the saccharin cue and the propensity to self-administer cocaine were maintained after at least 1 month of abstinence. As such, this paradigm may be useful as a model of cue-induced craving and drug-induced devaluation of natural rewards.

Reward comparison: the Achilles’ heel and hope for addiction

“…Were the animal in a state of cue-induced craving and/or withdrawal, the best correction for the onset of this aversive state would be drug. In accordance, and as discussed, greater avoidance of the taste cue and greater aversive taste reactivity was associated with a shorter latency to take drug, greater load-up, greater drug-taking, more rapid acquisition of drug self-administration and greater drug-seeking [8,76 ]. Future studies will need to track the development of this conditioned compensatory response to determine how various factors might affect the individual propensity for drug-induced devaluation, cue-induced craving/ withdrawal, drug-taking and drug-seeking over time.…”

“…The key, then, is to understand the conditions under which drugs devalue natural rewards and, alternatively, the conditions under which natural rewards might serve to protect against substance abuse and addiction. To this end, we continue to hone the first animal model for the systematic study of drug-induced devaluation of natural rewards [7,8 ]. We will describe this model and discuss what has been learned about devaluation, drug-taking, and the potential protective effects of natural rewards on substance abuse, addiction, and relapse.…”

Subjective sensitivity to monetary gradients is associated with frontolimbic activation to reward in cocaine abusers

“…Animal research suggests that after chronic drug administration the value of a drug reward is increased (Ahmed and Koob, 1998;Ahmed et al, 2002) while that of a non-drug reward is decreased (Grigson and Twining, 2002). Parallel human studies have generally reached similar conclusions.…”

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

“…Drugs k Dopaminergic transmission in the NAc and other mesolimbic reward pathways (Solomon and Corbit, 1974;Koob and Le Moal, 2001) k Motivation towards normally pleasurable stimuli (Grigson and Twining, 2002) k Activity in the NAc and other mesolimbic reward pathways Little et al, 1999;MartinSoelch et al, 2001a;Martin-Soelch et al, 2001b;Martin-Solch et al, 2001;Volkow et al, 2002a) Anhedonia and other negative affective states (Gawin and KhalsaDenison, 1996;Koob and Le Moal, 2001) commonly occurring in the setting of cortisol decreases during SGAs treatment Mann et al, 2006).…”

“…Prefrontal cortex (PFC) modulates these effects via reciprocal innervation with the hypothalamic-limbic areas (Berthoud, 2004a) by forming subjective hedonic perceptions and integrating them with metabolic signals and with intrapsychic and environmental contexts (Kringelbach, 2005). For the clarity of presentation, the scheme was rendered out-of-scale and simplified to reduce the numbers of the displayed links and structures to those of direct relevance to the main themes of this review.Eating and reward in schizophrenia I Elman et al K Self-administration of electric shock (Barrett and Spealman, 1978) K Stress-induced place preference (Bozarth, 1987) m Activity in the NAc and other mesolimbic reward pathways (Phillips et al, 1998;Becerra et al, 2001) K Leads to drug abuse and relapse (Sinha, 2001) K Seeking of mild-to-moderate stress (ie, roller coaster, automobile racing, skydiving, horror movies, etc) perceived as pleasant (Selye, 1976;Goeders, 2002) Drugs mDopaminergic transmission in the NAc and other mesolimbic reward pathways (Hernandez and Hoebel, 1988) Reinstatement of drug seeking and drug self-administration (Shaham et al, 2002) m Activity in the NAc and other mesolimbic reward pathways (Breiter et al, 1997;Volkow et al, 2002b) Mood elevation (Breiter et al, 1997) Chronic Stress kDopaminergic transmission in the NAc and other mesolimbic reward pathways (Puglisi-Allegra et al, 1991;Imperato et al, 1993) k Motivation towards normally pleasurable stimuli (eg, k sucrose consumption, animal homolog of anhedonia; Willner et al, 1987;Papp et al, 1991) k In reward function (Elman et al, 2005) Emotional numbing and anhedonia (American Psychiatric Association, 2000)Drugs k Dopaminergic transmission in the NAc and other mesolimbic reward pathways (Solomon and Corbit, 1974;Koob and Le Moal, 2001) k Motivation towards normally pleasurable stimuli (Grigson and Twining, 2002) k Activity in the NAc and other mesolimbic reward pathways Little et al, 1999; MartinSoelch et al, 2001a;…”