Incubation of cocaine craving after withdrawal

Incubation of cocaine craving after withdrawal

2001 July 12 | Jeffrey W. Grimm, Bruce T. Hope, Roy A. Wise, and Yavin Shaham
This study investigates the incubation of cocaine craving after withdrawal in laboratory rats, providing behavioral evidence that craving increases over a two-month withdrawal period. Rats were trained to press a lever for intravenous cocaine injections and then tested under conditions where cocaine was no longer available. Lever-pressing dropped to near zero ('extinguished') but could be temporarily reinstated by drug injections, stress, or drug-associated cues. After 10 days of training, rats were withdrawn from cocaine for varying durations (1, 2, 4, 7, 15, 29, or 60 days). During withdrawal, the lever was retracted and the house light was turned off. In the first test, resistance to extinction was measured in the presence of cues that indicated drug availability. Lever-pressing was minimal after one day of deprivation and maximal after 60 days. In the second test, cue-induced reinstatement was assessed 5 minutes after extinction. Lever-pressing was again minimal after one day and maximal after 60 days. The results show a linear increase in sensitivity to drug-associated cues over two months of withdrawal, consistent with clinical observations in humans. The study suggests that a delayed-onset craving syndrome develops during the first two months of cocaine abstinence and may last longer. The intensification of cocaine seeking occurs when most neuroadaptations from chronic cocaine use are in decline. The time course of this intensified drug seeking is similar to psychostimulant sensitization, which becomes stronger with increasing abstinence. The findings challenge the view that cocaine craving decays after drug cessation, instead suggesting that individuals are most vulnerable to relapse well beyond the acute phase of withdrawal.This study investigates the incubation of cocaine craving after withdrawal in laboratory rats, providing behavioral evidence that craving increases over a two-month withdrawal period. Rats were trained to press a lever for intravenous cocaine injections and then tested under conditions where cocaine was no longer available. Lever-pressing dropped to near zero ('extinguished') but could be temporarily reinstated by drug injections, stress, or drug-associated cues. After 10 days of training, rats were withdrawn from cocaine for varying durations (1, 2, 4, 7, 15, 29, or 60 days). During withdrawal, the lever was retracted and the house light was turned off. In the first test, resistance to extinction was measured in the presence of cues that indicated drug availability. Lever-pressing was minimal after one day of deprivation and maximal after 60 days. In the second test, cue-induced reinstatement was assessed 5 minutes after extinction. Lever-pressing was again minimal after one day and maximal after 60 days. The results show a linear increase in sensitivity to drug-associated cues over two months of withdrawal, consistent with clinical observations in humans. The study suggests that a delayed-onset craving syndrome develops during the first two months of cocaine abstinence and may last longer. The intensification of cocaine seeking occurs when most neuroadaptations from chronic cocaine use are in decline. The time course of this intensified drug seeking is similar to psychostimulant sensitization, which becomes stronger with increasing abstinence. The findings challenge the view that cocaine craving decays after drug cessation, instead suggesting that individuals are most vulnerable to relapse well beyond the acute phase of withdrawal.
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Understanding Neuroadaptation%3A Incubation of cocaine craving after withdrawal