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Positive affective vocalizations during cocaine and sucrose self-administration: a model for spontaneous drug desire in rats.

ABSTRACT: Ultrasonic vocalizations in the 50 kHz range (50 kHz USVs) are emitted by rodents upon activation of positive affective states and appear to be a direct measure of internal emotional and motivational urges to seek rewarding stimuli such as drugs of abuse. Since these behavioral responses do not rely on training for expression, they can be viewed as a "spontaneous" measure of affective state. The goal of the present study was to monitor spontaneous USVs throughout a widely-used cocaine self-administration and reinstatement model of addiction and relapse. To gain insight into the changes in affective state across the different phases of a standard self-administration experiment, we measured 50 kHz USVs in rats during cocaine self-administration and reinstatement, and compared these to sucrose self-administration and reinstatement. During cocaine self-administration, the number of 50 kHz USVs increased over acquisition of self-administration and decreased during extinction. Furthermore, the number of USVs on the first day of acquisition in the cocaine experiment was positively correlated with how rapidly cocaine self-administration was acquired. These findings suggest that the initial affective response to cocaine may be a sensitive predictor of the motivational efficacy of rewarding stimuli and therefore the susceptibility to acquire self-administration of cocaine. Cue- and cocaine-induced reinstatement elevated 50 kHz USVs above extinction levels. Rats trained for sucrose self-administration showed no elevation in USVs during acquisition when USVs were considered over the entire 2 h session, but they did show an elevation in USVs during acquisition when considered over only the first 5 min of the session. As with cocaine-induced reinstatement, sucrose-induced reinstatement produced significantly more USVs compared to the prior extinction day. Taken together, USVs may serve as a sensitive and dynamic non-invasive measure that spontaneously (i.e. without any formal reinforcement contingencies) quantifies the extent to which positive affect is elicited by rewards such as drugs of abuse.

SUBMITTER: Browning JR

PROVIDER: S-EPMC3115664 | biostudies-literature | 2011 Jul-Aug

REPOSITORIES: biostudies-literature

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Positive affective vocalizations during cocaine and sucrose self-administration: a model for spontaneous drug desire in rats.

Browning Jenny R JR Browning Douglas A DA Maxwell Alexis O AO Dong Yan Y Jansen Heiko T HT Panksepp Jaak J Sorg Barbara A BA

Neuropharmacology 20110421 1-2

Ultrasonic vocalizations in the 50 kHz range (50 kHz USVs) are emitted by rodents upon activation of positive affective states and appear to be a direct measure of internal emotional and motivational urges to seek rewarding stimuli such as drugs of abuse. Since these behavioral responses do not rely on training for expression, they can be viewed as a "spontaneous" measure of affective state. The goal of the present study was to monitor spontaneous USVs throughout a widely-used cocaine self-admin ...[more]

PMID: 21530553

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Project description:Sensation/novelty-seeking is amongst the best markers of cocaine addiction in humans. However, its implication in the vulnerability to cocaine addiction is still a matter of debate, as it is unclear whether this trait precedes or follows the development of addiction. Sensation/novelty-seeking trait has been identified in rats on the basis of either novelty-induced locomotor activity (high-responder (HR) trait) or novelty-induced place preference (high-novelty-preference trait (HNP)). HR and HNP traits have been associated with differential sensitivity to psychostimulants. However, it has recently been demonstrated that HR rats do not develop compulsive cocaine self-administration (SA) after protracted exposure to the drug, thereby suggesting that at least one dimension of sensation/novelty seeking in the rat is dissociable from the vulnerability to switch from controlled to compulsive cocaine SA. We therefore investigated whether HNP, as measured as the propensity to choose a new environment in a free choice procedure, as opposed to novelty-induced locomotor activity, predicts the vulnerability to, and the severity of, addiction-like behavior for cocaine. For this, we identified HR/LR rats and HNP/LNP rats before any exposure to cocaine. After 60 days of cocaine SA, each rat was given an addiction score based on three addiction-like behaviors (persistence of responding when the drug is signaled as not available, high breakpoint under progressive ratio schedule and resistance to punishment) that resemble the clinical features of drug addiction, namely inability to refrain from drug seeking, high motivation for the drug and compulsive drug use despite adverse consequences. We show that, as opposed to HR rats, HNP rats represent a sub-population predisposed to compulsive cocaine intake, displaying higher addiction scores than LNP rats. This study thereby provides new insights into the factors predisposing to cocaine addiction, supporting the hypothesis that addiction is sustained by two vulnerable phenotypes: a 'drug use prone' phenotype such as HR which brings an individual to develop drug use and an 'addiction prone' phenotype, such as HNP, which facilitates the shift from sustained to compulsive drug intake and addiction.

Dataset Information

Positive affective vocalizations during cocaine and sucrose self-administration: a model for spontaneous drug desire in rats.

Publications

Positive affective vocalizations during cocaine and sucrose self-administration: a model for spontaneous drug desire in rats.

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