Short communicationCorticotropin-releasing factor receptor type 1 mediates stress-induced relapse to cocaine-conditioned place preference in rats
Introduction
In individuals with a history of drug abuse, relapse to drug taking, even after prolonged periods of abstinence, is highly probable and remains the most difficult challenge for treatment. In both humans and nonhumans, acute re-exposure to the drug is a potent event for provoking relapse to drug-seeking behavior (Piazza and Le Moal, 1997). In addiction, exposure to stress, an event long thought to be important for relapse in humans, can induce relapse to opiate- and psychostimulant-seeking behavior in rats Erb et al., 1998, Stewart, 2000.
The mechanisms involved in the effect of stress on reinstatement of drug seeking are not understood, but corticotropin-releasing factor (CRF) plays a critical role in the neurobiological changes of stress that may leave individuals vulnerable to relapse Sarnyai et al., 1995, Koob and Heinrichs, 1999. CRF is a 41-amino acid peptide initially identified as a hypothalamic factor responsible for stimulating corticotropin (ACTH) secretion from the anterior pituitary Vale et al., 1981, Cummings et al., 1983. There is evidence that CRF is widely distributed throughout the central nervous system (CNS), where it induces various behavioral changes related to adaptation to stress. These include suppression of food intake, increase in locomotor activity and grooming in familiar environments, induction of aggression, and enhancement of arousal. α-Helical CRF, a nonspecific CRF receptor antagonist, may attenuate these behavioral effects Koob et al., 1994, DeVries et al., 1998, Basso et al., 1999. Recently, two CRF receptor subtypes, CRF receptor subtype 1 and CRF receptor subtype 2, were cloned and characterized in rats Perrin et al., 1993, Lovenberg et al., 1995. Subsequently, the pharmacological specificity and regional localization of these CRF receptor subtypes have been determined. CRF1 receptor shows a high affinity for CRF, while CRF2 receptor shows a lower affinity Grigoriadis et al., 1996, Radulovic et al., 1999. Both CRF1 and CRF2 receptors are widely and heterogeneously distributed in the central nervous system, suggesting distinctive functional roles for each receptor in the CRF-related system Lovenberg et al., 1995, Jasnow et al., 1999.
There is considerable evidence that CRF is involved in the anxiogenic and aversive effects of withdrawal from abused drugs, such as cocaine (Basso et al., 1999). Evidence also exists that administration of a CRF1 receptor antagonist attenuates stress-induced reinstatement of drug seeking Shaham et al., 1998, Lu et al., 2000a. However, the role of CRF1 and CRF2 receptors in stress-induced relapse to cocaine dependence remains unclear. In this study, we investigated the possible effects of CP-154,526 (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-ethylamine), a specific CRF1 receptor antagonist, and AS-30 ([d-Phe11,His12]Svg-(11-40)), a specific CRF2 receptor antagonist, and their differences in the induction of relapse to cocaine dependence induced by footshock stress.
Section snippets
Animal and drugs
Male Sprague–Dawley rats (body weight 250–280 g) were housed in the experimental animal center and maintained on a 12-light/dark cycle with access to food and water ad libitum. All animal treatments were strictly in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The drugs used were α-helical CRF (Sigma, USA), CP-154,526 (Pfizer, USA), AS-30 (Huasheng, China) and cocaine (Qinghai Pharmaceutical, China).
Intracerebroventricular cannulae
The cannula was implanted 5 days before
Results
In our pilot study, we designed a control group of animals that received injection of saline instead of cocaine (days 1, 3 and 5) and saline (days 2, 4 and 6) for six consecutive days. The results showed that these animals did not show place preference for any compartment on day 7 and also did not acquire place preference induced by a single injection of 10 mg/kg cocaine on day 38 (data not shown). However, alternate injection of cocaine (10 mg/kg) and saline for 6 days significantly increased
Discussion
Environmental stress has an important effect on the sensitivity of an individual to abused drugs. Studies of drug self-administration in laboratory animals have shown that both physical and psychological stressors facilitate the acquisition of drug self-administration, probably by increasing the reinforcing efficacy of abused drugs. Stressors also facilitate the reinstatement of drug taking even after prolonged periods of withdrawal Stewart, 1984, Piazza and Le Moal, 1997. For example, social
Acknowledgements
The authors wish to think Dr. Pen Xia and Zhiyuan Liu for their technical assistance. The work was supported in part by grants from the Ministry of Education and The Ministry of Public Health of China. All procedures were approved by the Animal Use Committee of the Ministry of Public Health of China and were in accordance with NIH Guidelines.
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2021, Neurobiology of StressCitation Excerpt :Acute administration of CRF reinstates cocaine seeking in male and female rats with a high degree of individual variability, though females overall show greater sensitivity (Buffalari et al., 2012a). Not surprisingly, administration of nonspecific CRF receptor antagonists (Astressin, α-helical CRF, D-Phe CRF12–41) consistently block stress-induced reinstatement of cocaine (Brown et al., 2009; Erb et al., 1998; Lu et al., 2001), methamphetamine (Nawata et al., 2012), and heroin seeking (Shaham et al., 1997; Shalev et al., 2006). This is likely through CRF receptor 1 (CRFR1) activity: specific CRFR1 antagonists block stress-induced reinstatement of cocaine-conditioned place preference (Lu et al., 2001; McReynolds et al., 2014; Shaham et al., 1998; Vranjkovic et al, 2014, 2018) while a specific CRFR2 antagonist (AS-30) fails to do so (Lu et al., 2001).
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