Abstract
Studies using either continuous or intermittent access cocaine self-administration procedures showed that cocaine seeking increases during abstinence (incubation of cocaine craving), and that this effect is higher after intermittent cocaine access. Other studies showed that cocaine abstinence is characterized by the emergence of stress- and anxiety-related states which were hypothesized to increase relapse vulnerability. We examined whether incubation of cocaine craving and anxiety-related behaviors are correlated and whether intermittent cocaine self-administration would potentiate these behaviors during abstinence. Male rats self-administered cocaine either continuously (6 h/day) or intermittently (5 min ON, 25 min OFF × 12) for 14 days, followed by relapse tests after 1 or 21 abstinence days. A group of rats that self-administered saline served as a control. Anxiety-related behaviors were measured on the same abstinence days, using the novelty induced-hypophagia test. Finally, motivation for cocaine was measured using a progressive ratio reinforcement schedule. Lever-presses after 21 abstinence days were higher than after 1 day and this incubation effect was higher in the intermittent access group. Progressive ratio responding was also higher after intermittent cocaine access. Intermittent and continuous cocaine access did not induce anxiety-like responses in the novelty-induced hypophagia test after 1 or 21 abstinence days. Independent of the access condition, incubation of cocaine seeking was not correlated with the novelty-induced hypophagia measures. Results suggest that cocaine-induced anxiety-related states during protracted abstinence do not contribute to incubation of cocaine craving. However, this conclusion is tentative because we used a single anxiety-related measure and did not test female rats.
Highlights
Persistent high rate of relapse is a main characteristic of drug addiction and one of the major obstacles in drug addiction treatment (Hunt et al, 1971; Sinha, 2011)
In the present study, we examined whether incubation of cocaine craving and anxietyrelated states are correlated and whether intermittent cocaine self-administration would potentiate these behaviors during abstinence
We further examined the relationship between anxiety-related behaviors and incubation of cocaine craving
Summary
Persistent high rate of relapse is a main characteristic of drug addiction and one of the major obstacles in drug addiction treatment (Hunt et al, 1971; Sinha, 2011). In rats with continuous cocaine self-administration history, non-reinforced cocaine seeking in the presence of drug-associated cues and contexts progressively increases during forced abstinence (Neisewander et al, 2000; Grimm et al, 2001; Chauvet et al, 2012), a phenomenon termed incubation of cocaine craving (Lu et al, 2004; Pickens et al, 2011). Two studies using the novelty-induced hypophagia test (Dulawa et al, 2004) showed that paternal but not maternal cocaine self-administration increases anxiety-related behaviors in male, but not female, offspring (White et al, 2016; Fant et al, 2019) Together, these clinical and preclinical studies suggest that exposure to cocaine-associated cues and anxiety-related states during abstinence contribute to relapse vulnerability. We measured on abstinence day 22 the motivation to self-administer cocaine using a progressive ratio reinforcement schedule (Richardson and Roberts, 1996)
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