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Interactions of Social Behavior and Treatment Drugs on Cocaine Self- Administration This review has highlighted several examples of dominant and subordinate animals being differentially sensitive to the behavior-altering effects of drugs. Methadone treated patients show withdrawal symptoms when exposed to metyrapone[ 44 ]. Some examples of environmental manipulations hypothesized to shift the curve to the left stressors and to the right enrichers are provided. However, based on the studies in monkeys described in this review, it is clear that the pharmacological consequences of treatment drugs may be different depending on the social experiences of the individual. Czoty1 Susan H. Rapid delivery may lead some people to use more cocaine more often and, hence, more easily losing control over their use. It was postulated by the authors that patients randomized to ketoconazole may have been self-medicating to minimize the adverse effects of the study drug, including dyspepsia, nausea and body aches. Data discussed in the next section indicate that social status can prominently influence the abuse-related behavioral effects of cocaine. All monkeys clearly exhibited a fear-like reaction to the presence of the snake, retreating to the opposite end of the test cage. Abnormal adrenal gland metabolism in opioid addicts: Pituitary-gonadal function in heroin addicts. Changes in HPA dynamics lead to cravings and relapse behavior. Animals are individually housed, lighting conditions remain the same for every experiment and a stable body weight is maintained. That is, although like males, dominant female monkeys had higher D2-like receptor measures than subordinate females, the dominant females were more sensitive to the reinforcing effects of cocaine. National Center for Biotechnology InformationU. What is particularly striking about the conclusion regarding whether a social rank is stressful is that it appears to vary according to the dependent variable under study. Cocaine, social behavior, and alcohol-solution drinking in monkeys. In group-housed monkeys, social subordination has been characterized as stressful e. The following dependent variables are examined: Dominant macaques freely move throughout the pen without fear of aggression, are groomed and submitted to more frequently, and have first access to food or treats within the pen Morgan et al. A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men. Laser on aggravated possession of drugs, possession of drugs. Heightened aggressive behavior by animals interacting with alcohol-treated conspecifics: However, the administration of metyrapone increased HPA activity in cocaine users, illustrating different effects of opiates and stimulants on HPA function. Handbook of Social Neuroscience. One could hypothesize that if cocaine-induced aggression by the subordinate monkey changed his position in the hierarchy, this may initially increase the reinforcing effects of cocaine because the change in social rank is a consequences associated with cocaine use. Hypercortisolism after opioid discontinuation in rapid detoxification of heroin addicts. Potential consequences of adrenal and gonadal abnormalities Depression, stress, quality of life and cognition Hypogonadism and adrenal dysfunction can have important effects on mood and cognition. In addition, the ability to study the same subjects for years allows for within-subject assessments of multiple independent variables Nader et al. The extent to which depressive symptoms in drug users are related to abnormalities in the HPG or HPA axes has not been clarified. Perhaps what was most striking was that the most affected monkeys, both in terms of increases in cocaine intake and increases in cocaine-induced aggression, were the intermediate-ranked monkeys. Intl J Impot Res. In an animal model of cocaine addiction, binge cocaine administration to rats caused decreased testosterone concentrations[ 16 ]. Whereas the manipulations described above were expected to function as either stressors or enrichers in all monkeys regardless of social rank, two other interventions were conducted that were hypothesized to have differential effects depending on the social rank of the monkey. Opiates and cocaine both have effects on adrenal and gonadal function. During drug withdrawal, some studies have shown activation of the HPA axis, possibly contributing to relapse behavior. Shepherd aka Shawn Shepard aka Shawn A. Oxford University Press, Inc; Leftward shift in the acquisition of cocaine self-administration in isolation-reared rats: Interestingly, male monkeys have a more robust HPA response to cocaine use compared to females[ 24 ] however in rats, females exhibit a greater HPA response to cocaine than males. Davis on tampering with evidence, indicted on other charges. The goals of these studies were to 1 examine the effects of social consequences i. Hypogonadism and adrenal dysfunction can have important effects on mood and cognition. Ritter II on possession of heroin. Mood abnormalities can have important repercussions on drug abuse behavior, in that drug dependent individuals with depression are more like to be unsuccessful in attempts to abstain[ 32 ]. Although the mechanism has not been fully clarified, animal models suggest that testosterone and estrogen have direct effects on central serotonergic receptors[ 26 ]. Proc Natl Acad Sci. By day 4 and for the remainder of the study 12 weeksthere were no differences in cortisol concentrations as a function of social rank.

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For example, we have noted in socially housed cynomolgus monkeys that the behavioral effects of DA receptor agonists appear to be influenced by social rank, while those of DA antagonists are not. The validity of the reinstatement model of craving and relapse to drug use. In contrast to prior animal studies, ketoconazole failed to suppress plasma cortisol concentrations. In vitro human neuronal cultures that include neurotoxic HIV proteins and exposed to a variety of stimulants such as cocaine were protected from the neurotoxic effects of the drugs by treatment with estrogen. Additionally, there is a large literature concerning the modulatory effects of sex steroid hormones on cognition in people who are neither HIV-infected nor drug users. Cortical activation during cocaine use and extinction in rhesus monkeys. It was postulated by the authors that patients randomized to ketoconazole may have been self-medicating to minimize the adverse effects of the study drug, including dyspepsia, nausea and body aches. This represented a novel situation for the monkeys because standard operating procedure is to separate monkeys for approximately 90 min each day for feeding to assure that all monkeys in the pen receive adequate food. Stress, vulnerability and adult alcohol relapse. Neuroendocrine-related effects of long-term, 'binge' cocaine administration: One of the premises of behavioral pharmacology is that the effects of drugs on behavior maintained by different events can be differentially affected by some drugs, but not by all drugs Barrett and Katz, However, basal cortisol levels did not differ between dominant and subordinate cynomolgus monkeys. Effects of cocaine on luteinizing hormone in women during the follicular and luteal phases of the menstrual cycle and in men. A better understanding of the neurobiological mechanisms underlying these differences may provide insight into treatment strategies Miczek and de Almeida Testosterone regulates pro-opiomelanocortin gene expression in the primate brain. Each of these variables has a level of complexity, including the history of the individual both behavioral and pharmacologicalenvironmental context, and genetics. Are subordinates always stressed? In many of these studies, individually housed rats are compared to rats housed in social groups with enrichment objects placed in the cage. In humans, however, a randomized, placebo-controlled trial of ketoconazole in methadone maintained patients failed to show any benefit on illicit drug use behavior. In general, cocaine and amphetamine decreased most forms of social behavior, including aggression. Arch Periatr Adolesc Med. The social experiences of intermediate-ranked monkeys, and the effects of those experiences on physiology and behavior, are almost completely overlooked in favor of focusing on the most dominant and most subordinate monkeys, but it is clear that they are extremely relevant and should be studied in greater detail. They reported large species differences in basal cortisol concentrations, with subordinate monkeys having either higher, lower or no difference than dominant monkeys Abbott et al. There is also a growing body of literature examining the direct and indirect effects of psychoactive drugs on social behaviors e. Effects of environmental conditions on food consumption in female and male rats. The studies reviewed here indicate that several variables can differentially affect cocaine self-administration when studied in a social context, rather than in individually housed animals. Given these findings, what is different about C and C that could account for such disparate results? In a study of detoxified heroin addicts, intravenous administration of heroin 10 mg produced acute suppression of LH secretion, leading to reduced testosterone concentration with a peak effect after 4—6 hours[ 6 ]. Exogenously administered opioids also inhibit GnRH secretion, resulting in HPG dysfunction at the level of the hypothalamus. As observed previously Paronis et al. This review will focus on the extent to which the HPG and HPA axes are altered with exposure to opiates and cocaine and the potential for these changes to lead to depression, reduced quality of life and illness. Screening for depressive symptoms among HCV-infected injection drug users: Given the potential role of HPA and HPG axis abnormalities in craving and relapse in drug dependent subjects, these endocrine systems may provide a target to improve drug treatment. Effects of testosterone administration on fat distribution, insulin sensitivity and atherosclerosis progression. Relationship between all-cause mortality and cumulative working life course psychosocial and physical exposures in the United States labor market from to However, certain translational questions can only be answered using experimental designs incorporating situations in which animals behave in a social environment. As Barrett and Miczek stated: Furthermore, subordinate cynomolgus monkeys have heavier adrenal glands compared to dominant monkeys Shively and Kaplan Impairment of ovarian function and associated health-related abnormalities are attributable to low social status in premenopausal monkeys and not mitigated by a high-isoflavone soy diet. J Pharmacol Exp Ther. Such results support the view that, whereas most individuals can manage the many minor inconveniences we all encounter on a daily basis, such experiences appear to be much more stressful in certain people which subsequently makes them more likely to abuse cocaine.

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