Stress and Cocaine Addiction

Abstract

The hypothalamo-pituitary-adrenal (HPA) axis is involved in all aspects of cocaine self-administration. Corticosterone seems to be crucial for the acquisition of drug use since self-administration does not occur unless this stress hormone is increased above a critical reward threshold. Increasing circulating levels of corticosterone also augments sensitivity to low doses of cocaine, possibly from a sensitization-associated phenomenon involving dopamine, suggesting that exposure to stress can increase individual vulnerability to cocaine. Drugs affecting the synthesis and/or secretion of corticosterone decrease ongoing, low-dose cocaine self-administration. When higher doses falling on the descending limb of the cocaine dose-response curve are self-administered, plasma corticosterone can still reach this reward threshold even when synthesis is inhibited and drug intake is not affected. Corticotropin-releasing hormone (CRH) seems to play a more prominent role in the maintenance of cocaine self-administration and may even be involved in the incentive motivation for the drug. Corticosterone and CRH are also critical for the stress-and cue-induced reinstatement of extinguished cocaine-seeking behavior. Therefore, cocaine self-administration may represent an attempt to seek out specific sensations, with the internal state produced being very similar to that perceived by individuals who engage in risky, thrill-seeking behavior. During abstinence, exposure to stressors or cocaine-associated cues can stimulate the HPA axis to remind the individual about the effects of cocaine, thus producing craving and promoting relapse. Stress reduction, either alone or in combination with pharmacotherapies targeting the HPA axis may prove beneficial in reducing cravings and promoting abstinence in individuals seeking treatment for cocaine addiction.The role of stress and the subsequent activation of the hypothalamo-pituitary-adrenal (HPA) axis in drug addiction has been under investigation in a number of laboratories for several years now. Subsequently, a number of excellent review articles have recently been published in an attempt to summarize the relevant research findings and to provide a rational explanation for these data

Higher locomotor response to cocaine in female (vs. male) rats selectively bred for high (HiS) and low (LoS) saccharin intake

“…Other mechanisms that could explain the phenotype and sex differences described here, and in related studies, are sensitivity to stress (Goeders 2002), the rate of learning and ability to perform the operant task (Mitchell et al, 2005), the ability to associate stimuli with the reward, and other traits such as impulsivity for the reward (Dalley et al 2007;Perry et al, 2005Perry et al, , 2007b. Future investigations of the unique behavioral and neurobiological characteristics of the HiS and LoS and other reward-seeking-prone-and resistant animals could provide information on the mechanisms underlying the interrelated findings and complex interactions that have emerged.…”

Elevation of Glucocorticoids is Necessary but not Sufficient for the Escalation of Cocaine Self-Administration by Chronic Electric Footshock Stress in Rats

“…Pre-clinical findings from studies using rodent models further support a role for stress in cocaine abuse (see Goeders (2002) for review). A number of investigators have demonstrated that stressors facilitate the acquisition of cocaine SA (see eg Goeders and Guerin, 1994;Haney et al, 1995;Miczek and Mutschler, 1996;Ramsey and Van Ree, 1993;Campbell and Carroll, 2001;Kosten et al, 2000;Schenk et al, 1987) and reinstate extinguished cocaine-seeking behavior (Erb et al, 1996;Ahmed and Koob, 1997;Mantsch and Goeders, 1999a;Shalev et al, 2003).…”

Systemic ghrelin sensitizes cocaine-induced hyperlocomotion in rats

“…Stressors, including FR, are known to induce the release of ACTH and corticosterone and induce a degree of sensitization in dopamine signaling pathways (Broocks et al, 1990;Goeders, 2002a;2002b;Marinelli et al, 1997;Rouge-Pont et al, 1995). ICV administration of ghrelin activates the HPA axis increasing ACTH and corticosterone (Stevanovic et al, 2007;Wren et al, 2001b).…”