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Self-administration Sessions (self-administration + session)
Selected AbstractsEffects of Neuropeptide Y on Appetitive and Consummatory Behaviors Associated With Alcohol Drinking in Wistar Rats With a History of Ethanol ExposureALCOHOLISM, Issue 4 2005Annika Thorsell Background: Neuropeptide Y (NPY) reduces ethanol intake under free access conditions in Wistar rats with a history of prolonged ethanol vapor exposure. The current study was designed to determine whether NPY differentially alters ethanol-associated appetitive behavior (i.e., lever pressing) or ethanol consumption in Wistar rats with a history of ethanol vapor exposure. Methods: Wistar rats were first trained to self-administer 10% ethanol in a paradigm that provided 25 min of free access to 10% ethanol after completing a 20,lever press response requirement (i.e., an RR20 schedule). After stable level lever pressing was established, operant sessions were suspended during a 9-week period of ethanol vapor exposure. Self-administration sessions were then reinstituted, and a fixed time (FT) schedule of 10% ethanol access was used to assess the effects of ethanol exposure and NPY on lever pressing and drinking behavior. Under the FT schedule, the maximum number of lever presses emitted within 10 min was assessed before providing access to 10% ethanol. Results: Ethanol vapor exposure did not alter patterns of lever pressing under the RR20 schedule, but lever presses emitted under the FT schedule were reduced after ethanol vapor exposure. Ethanol intake was significantly increased after ethanol vapor exposure. NPY significantly reduced ethanol intake but did not significantly reduce lever pressing under the FT schedule. Conclusions: Taken together, these data suggest that chronic ethanol exposure increases ethanol intake without clearly enhancing its reinforcing value. Furthermore, NPY has a greater impact on the consummatory factors mediating ethanol intake than appetitive factors mediating ethanol seeking. [source] RESEARCH FOCUS ON COMPULSIVE BEHAVIOUR IN ANIMALS: Pre-exposure to environmental cues predictive of food availability elicits hypothalamic,pituitary,adrenal axis activation and increases operant responding for food in female ratsADDICTION BIOLOGY, Issue 4 2009Carlo Cifani ABSTRACT The present study was undertaken to develop an animal model exploiting food cue-induced increased motivation to obtain food under operant self-administration conditions. To demonstrate the predictive validity of the model, rimonabant, fluoxetine, sibutramine and topiramate, administered 1 hour before the experiment, were tested. For 5 days, female Wistar rats were trained to self-administer standard 45 mg food pellets in one daily session (30 minutes) under FR1 (fixed ratio 1) schedule of reinforcement. Rats were then trained to an FR3 schedule and finally divided into two groups. The first group (control) was subjected to a standard 30 minutes FR3 food self-administration session. The second group was exposed to five presentations of levers and light for 10 seconds each (every 3 minutes in 15 minutes total). At the completion of this pre-session phase, a normal 30-minute session (as in the control group) started. Results showed that pre-exposure to environmental stimuli associated to food deliveries increased response for food when the session started. Corticosterone and adrenocorticotropic hormone plasma levels, measured after the 15-minute pre-exposure, were also significantly increased. No changes were observed for the other measured hormones (growth hormone, prolactin, thyroid-stimulating hormone, luteinizing hormone, insulin, amylin, gastric inhibitor polypeptide, ghrelin, leptin, peptide YY and pancreatic polypeptide). Rimonabant, sibutramine and fluoxetine significantly reduced food intake in both animals pre-exposed and in those not pre-exposed to food-associated cues. Topiramate selectively reduced feeding only in pre-exposed rats. The present study describes the development of a new animal model to investigate cue-induced increased motivation to obtain food. This model shows face and predictive validity, thus, supporting its usefulness in the investigation of new potential treatments of binge-related eating disorders. In addition, the present findings confirm that topiramate may represent an important pharmacotherapeutic approach to binge-related eating. [source] REVIEW: Developing human laboratory models of smoking lapse behavior for medication screeningADDICTION BIOLOGY, Issue 1 2009Sherry A. McKee ABSTRACT Use of human laboratory analogues of smoking behavior can provide an efficient, cost-effective mechanistic evaluation of a medication signal on smoking behavior, with the result of facilitating translational work in medications development. Although a number of human laboratory models exist to investigate various aspects of smoking behavior and nicotine dependence phenomena, none have yet modeled smoking lapse behavior. The first instance of smoking during a quit attempt (i.e. smoking lapse) is highly predictive of relapse and represents an important target for medications development. Focusing on an abstinence outcome is critical for medication screening as the US Food and Drug Administration approval for cessation medications is contingent on demonstrating effects on smoking abstinence. This paper outlines a three-stage process for the development of a smoking lapse model for the purpose of medication screening. The smoking lapse paradigm models two critical features of lapse behavior: the ability to resist the first cigarette and subsequent ad libitum smoking. Within the context of the model, smokers are first exposed to known precipitants of smoking relapse (e.g. nicotine deprivation, alcohol, stress), and then presented their preferred brand of cigarettes. Their ability to resist smoking is then modeled and once smokers ,give in' and decide to smoke, they participate in a tobacco self-administration session. Ongoing and completed work developing and validating these models for the purpose of medication screening is discussed. [source] Intravenous heroin self-administration decreases GABA efflux in the ventral pallidum: an in vivo microdialysis study in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004Stéphanie Caillé Abstract Several lines of evidence suggest that opiate-induced disinhibition of the ventral pallidum participates in the mediation of opiate reward, though direct in vivo evidence to support this hypothesis has been lacking. The present experiment tested this hypothesis by investigating alterations in ventral pallidal amino acid efflux using in vivo microdialysis during ongoing intravenous heroin self-administration in rats. Concentrations of the inhibitory amino acid GABA in ventral pallidal dialysates were significantly reduced within the first 10 min of heroin self-administration (0.02 mg per infusion; FR-1), and remained ,,65% of presession baseline levels for the remainder of the 3-h self-administration session. Dialysate glutamate levels were unaltered during the first hour of heroin intake but significantly increased to a stable level of ,,120% presession values during the subsequent 2 h of self-administration. Thus, heroin self-administration is associated with both decreased GABA efflux and a late phase increase in glutamate efflux in the ventral pallidum. These observations are consistent with the hypothesis that heroin self-administration results in a disinhibition and/or excitation of the ventral pallidum. [source] PRECLINICAL STUDY: Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long- but not short-access ratsADDICTION BIOLOGY, Issue 2 2009Thomas N. Greenwell ABSTRACT Dysregulation of the stress-related corticotropin-releasing factor (CRF) system has been implicated in the development of drug dependence. The present study examined the effects of administering CRF type 1 (CRF1) receptor antagonists on heroin self-administration in animals allowed short (1 hour) or long (8,12 hours) access to intravenous heroin self-administration sessions. The nonpeptide CRF1 antagonists MJL-1-109-2 (1 hour versus 8 hours access) or R121919 (1 hour versus 12 hours access) were systemically injected in both short- and long-access rats. MJL-1-109-2 (10 mg/kg) and R121919 (10 and 20 mg/kg) reduced heroin self-administration in long-access animals without altering heroin intake in short-access animals. Both MJL-1-109-2 and R121919 decreased first-hour intravenous heroin self-administration selectively in long-access rats, with R121919 decreasing cumulative heroin intake across the 12-hour session. The results demonstrate that blockade of the CRF,CRF1 receptor system attenuates the increased heroin intake of rats with extended access to the drug. [source] Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine stateEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2008Heather N. Richardson Abstract Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but remaining unknown is whether functional differences in the hypothalamic-pituitary-adrenal (HPA) axis precede alcohol abuse and dependence or result from chronic exposure to this drug. Using an operant self-administration animal model of alcohol dependence and serial blood sampling, we show that long-term exposure to alcohol causes significant impairment of HPA function in adult male Wistar rats. Acute alcohol (voluntary self-administration or experimenter-administered) stimulated the release of corticosterone and its upstream regulator, adrenocorticotropic hormone, but chronic exposure sufficient to produce dependence led to a dampened neuroendocrine state. HPA responses to alcohol were most robust in ,low-responding' non-dependent animals (averaging < 0.2 mg/kg/session), intermediate in non-dependent animals (averaging ,0.4 mg/kg/session), and most blunted in dependent animals (averaging ,1.0 mg/kg/session) following several weeks of daily 30-min self-administration sessions, suggesting that neuroendocrine tolerance can be initiated prior to dependence and relates to the amount of alcohol consumed. Decreased expression of corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus and reduced sensitivity of the pituitary to CRF may contribute to, but do not completely explain, neuroendocrine tolerance. The present results, combined with previous studies, suggest that multiple adaptations to stress regulatory systems may be brought about by excessive drinking, including a compromised hormonal response and a sensitized brain stress response that together contribute to dependence. [source] Induction and Maintenance of Ethanol Self-Administration in Cynomolgus Monkeys (Macaca fascicularis): Long-Term Characterization of Sex and Individual DifferencesALCOHOLISM, Issue 8 2001J. A. Vivian Background: Investigations of oral ethanol self-administration in nonhuman primates have revealed important parallels with human alcohol use and abuse, yet many fundamental questions concerning the individual risk to, and the biological basis of, excessive ethanol consumption remain unanswered. Moreover, many conditions of access to ethanol in nonhuman primate research are largely unexplored. This set of experiments extends within- and across-session exposure to ethanol to more fully characterize individual differences in oral ethanol self-administration. Methods: Eight male and eight female adult cynomolgus monkeys (Macaca fascicularis) were exposed to daily oral ethanol self-administration sessions for approximately 9 months. During the first 3 months, a fixed-time (FT) schedule of food delivery was used to induce the consumption of an allotted dose of ethanol in 16-hr sessions. Subsequently, the FT schedule was suspended, and ethanol was available ad libitum for 6 months in 16- or 22-hr sessions. Results: Cynomolgus monkeys varied greatly in their propensity to self-administer ethanol, with sex and individual differences apparent within 10 days of ethanol exposure. Over the last 3 months of ethanol access, individual average ethanol intakes ranged from 0.6 to 4.0 g/kg/day, resulting in blood ethanol concentrations from 5 to 235 mg/dl. Males drank approximately 1.5-fold more than females. In addition, heavy-, moderate-, and light-drinking phenotypes were identified by using daily ethanol intake and the percentage of daily calories obtained from ethanol as criteria. Conclusions: Cynomolgus monkeys displayed a wide intersubject range of oral ethanol self-administration with a procedure that used a uniform and prolonged induction that restricted early exposure to ethanol and subsequently allowed unlimited access to ethanol. There were sex and stable individual differences in the propensity of monkeys to consume ethanol, indicating that this species will be important in characterizing risk factors associated with heavy-drinking phenotypes. [source] Effect of Naloxone on Appetitive and Consummatory Phases of Ethanol Self-AdministrationALCOHOLISM, Issue 7 2001Amanda L. Sharpe Background : The opioid system has been implicated in ethanol self-administration. Morphine, an opiate agonist, can sometimes increase the amount of ethanol consumed, and opiate antagonists such as naloxone and naltrexone decrease the amount of ethanol consumed in both animals and humans. The objective of this study was to examine the effect of naloxone on appetitive (or seeking) and consummatory behaviors by using an operant model developed to separate these two phases of self-administration. Methods: Intraperitoneal injections of naloxone (0.3,10 mg/kg) or vehicle were given before operant self-administration sessions to assess the effect on lever pressing (appetitive behavior) and subsequent consumption. Effects were measured in two groups of rats: one self-administered a 3% sucrose solution and the other a 10% ethanol solution. Results: Naloxone dose-dependently decreased ethanol and sucrose consumption by an earlier cessation of drinking in the session compared with vehicle injection days. There were some effects on appetitive responding after treatment with naloxone, but none was statistically significant. Conclusions: Naloxone may decrease ethanol self-administration by decreasing the postingestive or pharmacological effects of alcohol. This model provides a new method for examining the effects of potential pharmacotherapeutics on alcohol self-administration behavior. [source] | ||||||||||