Stressor- and Corticotropin releasing Factor-induced Reinstatement and Active Stress-related Behavioral Responses are Augmented Following Long-access Cocaine Self-administration by Rats

Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness. Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA). Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and for behavioral responsiveness on the elevated plus maze, in a novel environment and in the light–dark box after a 14- to 17-day extinction/withdrawal period. Results LgA rats showed escalating patterns of cocaine SA and were more susceptible to reinstatement by cocaine, EFS, or icv CRF than ShA rats. Overall, cocaine SA increased activity in the center field of a novel environment, on the open arms of the elevated plus maze, and in the light compartment of a light–dark box. In most cases, the effects of cocaine SA were dependent on the pattern/amount of cocaine intake with statistically significant differences from saline self-administering controls only observed in LgA rats. Conclusions When examined after several weeks of extinction/ withdrawal, cocaine SA promotes a more active pattern of behavior during times of stress that is associated with a heightened susceptibility to stressor-induced cocaine-seeking behavior and may be the consequence of augmented CRF regulation of addiction-related neurocircuitry

Ultrasonic vocalization in rats self-administering heroin and cocaine in different settings: evidence of substance-specific interactions between drug and setting

Rationale Clinical and preclinical evidence indicates that the setting of drug use affects drug reward in a substance-specific manner. Heroin and cocaine co-abusers, for example, indicated distinct settings for the two drugs: heroin being used preferentially at home and cocaine preferentially outside the home. Similar results were obtained in rats that were given the opportunity to self-administer intravenously both heroin and cocaine. Objectives The goal of the present study was to investigate the possibility that the positive affective state induced by cocaine is enhanced when the drug is taken at home relative to a non-home environment, and vice versa for heroin. Methods To test this hypothesis, we trained male rats to self-administer both heroin and cocaine on alternate days and simultaneously recorded the emission of ultrasonic vocalizations (USVs), as it has been reported that rats emit 50-kHz USVs when exposed to rewarding stimuli, suggesting that these USVs reflect positive affective states. Results We found that Non-Resident rats emitted more 50-kHz USVs when they self-administered cocaine than when self-administered heroin whereas Resident rats emitted more 50-kHz USVs when self-administering heroin than when self-administering cocaine. Differences in USVs in Non-Resident rats were more pronounced during the first self-administration (SA) session, when the SA chambers were completely novel to them. In contrast, the differences in USVs in Resident rats were more pronounced during the last SA sessions. Conclusion These findings indicate that the setting of drug taking exerts a substance-specific influence on the ability of drugs to induce positive affective states

Adolescent Binge Drinking Leads to Changes in Alcohol Drinking, Anxiety, and Amygdalar Corticotropin Releasing Factor Cells in Adulthood in Male Rats

Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (∼postnatal days 28–42) in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF) cell in the lateral portion of the central amygdala (CeA), a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity), an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects with implications for anxiety and alcohol use disorders

Disulfiram Implantation in Alcohol Dependency: Influence of Sociodemographic and Clinical Variables on Treatment Response

Objective: Psychopharmacological, psychotherapeutic and psychosocial treatment methods are being used in alcohol dependence, which is a frequently occurring psychiatric disorder. In alcohol dependence, promising treatment strategies like naltrexone, acamprosate and topiramate are being tested and numerous research studies have been conducted about these novel drugs in recent years. The administration of disulfiram, which has been used for years, appears to be decreasing. Research on disulfiram implantation, which has been used since the 1950's, had been carried out in 1990's. Our aim with this retrospective study was to investigate the contribution of low cost disulfiram implantation to the treatment of individuals with alcoholism and the influence of sociodemographic and clinical characteristics on treatment response

Insula-specific 1H magnetic resonance spectroscopy reactions in heavy smokers under acute nicotine withdrawal and after oral nicotine substitution

The aim of this study was to clarify whether addiction-specific neurometabolic reaction patterns occur in the insular cortex during acute nicotine withdrawal in tobacco smokers in comparison to nonsmokers. Fourteen male smokers and 10 male nonsmokers were included. Neurometabolites of the right and the left insular cortices were quantified by magnetic resonance spectroscopy (MRS) on a 3-Tesla scanner. Three separate MRS measurements were performed in each subject: among the smokers, the first measurement was done during normal smoking behavior, the second measurement during acute withdrawal (after 24 h of smoking abstinence), and the third shortly after administration of an oral nicotine substitute. Simultaneously, craving, withdrawal symptoms, and CO levels in exhaled air were determined during the three phases. The participants in the control group underwent the same MR protocol. In the smokers, during withdrawal, the insular cortex showed a significant increase in glutamine (Gln; p = 0.023) as well as a slight increase not reaching significance for glutamine/glutamate (Glx; p = 0.085) and a nonsignificant drop in myoinositol (mI; p = 0.381). These values tended to normalize after oral nicotine substitution treatment, even though differences were not significant: Gln (p = 0.225), Glx (p = 0.107) and mI (p = 0.810). Overall, the nonsmokers (control group) did not show any metabolic changes over all three phases (p > 0.05). In smokers, acute nicotine withdrawal produces a neurometabolic reaction pattern that is partly reversed by the administration of an oral nicotine substitute. The results are consistent with the expression of an addiction-specific neurometabolic shift in the brain and confirm the fact that the insular cortex seems to play a possible role in nicotine dependence