mGluR5 positive allosteric modulation enhances extinction learning following cocaine self-administration.

Extinction of classically and instrumentally conditioned behaviors, such as conditioned fear and drug-seeking behavior, is a process of active learning, and recent studies indicate that potentiation of glutamatergic transmission facilitates extinction learning. In this study, the authors investigated the effects of the Type-5 metabotropic glutamate receptors (mGluR5) positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) on the extinction of cocaine-seeking behavior in rats with a history of intravenous cocaine self-administration. To assess its effects on acquisition and consolidation of extinction learning, CDPPB (60 mg/kg) or vehicle was administered either 20 min prior to, or immediately following, each of 10 extinction sessions, respectively. When administered prior to each extinction session, CDPPB produced a significant reduction in the number of active lever presses on all 10 days of extinction training as compared to vehicle-treated animals. When administered following each extinction session, a significant reduction in the number of active lever presses was observed on the 2nd through 10th day of extinction. Both treatment regimens also reduced the number of extinction-training sessions required to meet extinction criteria. Pre- or postextinction-training administration of CDPPB did not alter responding on the inactive lever and had no effects on open field locomotor activity. These data indicate that positive allosteric modulation of mGluR5 receptors facilitates the acquisition and consolidation of extinction learning following cocaine self-administration and may provide a novel pharmacological approach to enhancing extinction learning when combined with cue exposure therapy for the treatment of cocaine addiction. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Wheel-running behavior is altered following withdrawal from repeated cocaine in adult rats.

The residual effects on open-field habituation and self-generated wheel running following withdrawal from repeated cocaine (COC; 30 mg/kg for 7 days) were examined in adult male rats. Control subjects received equivolumetric injections of saline (SAL) and were either allowed to feed ad libitum or pair-fed matched (PF SAL) to COC subjects to control for the drug's potential anorexic effect. Following 10 days of withdrawal, all subjects were examined twice on each of the two assessment instruments. Results indicated that COC subjects over the two test sessions failed to increase their wheel-running rates and did not show the expected habituation in the open field. However, because both COC and PF SAL groups yielded similar effects in the open field, conclusions about cocaine's consequences on habituation could not be established independent of the drug's anorexic effect. These data provide evidence for the view that repeated cocaine impairs motivational processes responsible for engaging in self-generated naturally rewarding behaviors. Speculation concerning the neurobiobehavioral substrates for this effect is presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in energy balance following smoking cessation and resumption of smoking in women.

Caloric intake, resting metabolic rate (RMR), leisure-time physical activity, and sensitivity and preference for sweet taste were prospectively examined in 7 female smokers across 3 weeks during periods of normal smoking (Week 1), complete cessation (Week 2), and resumption of smoking (Week 3). Energy balance changed significantly across weeks, as caloric intake increased (largely as a result of alcohol consumption) and RMR decreased during cessation, followed by decreased caloric intake and increased RMR with resumption of smoking. Activity and taste sensitivity and preference remained unchanged. Smoking cessation may thus cause rapid change in energy balance, which is quickly reversed on resumption of smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning following repeated exposure to MDMA in rats: Role in the maintenance of MDMA self-administration.

There has been some controversy in the literature concerning the ability of ±3,4 methylenedioxymethamphetamine (MDMA) to reinforce operant responding in rats. In the present study, operant responding maintained by intravenous MDMA infusions increased when the fixed ratio schedule was increased from 1 to 5, decreased when saline was substituted for MDMA, and increased again when MDMA was reintroduced. During self-administration training, each infusion of MDMA was paired with the illumination of a light stimulus. The role of the continued presentation of this drug-associated stimulus in operant responding was measured in groups of rats that had received comparable exposure (average 19 daily test sessions) to MDMA during training. When either the light stimulus or the drug infusion was omitted, operant responding decreased gradually over the 15-day test period following training. When both the light stimulus and the MDMA infusion were omitted, there was a dramatic decrease in operant responding that persisted for the entire 15-day test period. These findings suggest that cues associated with MDMA develop conditioned properties that might contribute to drug taking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic cadmium exposure alters cocaine self-administration in adult male rats.

Adult male rats (Rattus norvegicus) were exposed to a water supply in the home cage containing 100 ppm cadmium chloride and sodium saccharin (.65% wt/vol; cadmium group) or water containing only the saccharin amendment (group control). On Day 65 of exposure, animals from each group received jugular catheter implants and were subsequently trained over the course of 15 daily 2-hr sessions to self-administer a .25 mg/kg/infusion of cocaine HCl under a fixed ratio 1 schedule. Immediately following acquisition training, the full dose-effect function was determined for all animals by using cocaine doses of .03, .06, .125, .25, .50, and 1.0 mg/kg. Cadmium-exposed animals executed more active (cocaine) lever responses during acquisition training but were not different from controls in depressing a pharmacologically inactive lever. For dose-effect testing, cadmium exposed animals exhibited greater self-administration than controls at the higher doses of cocaine, and there was evidence that the cocaine dose that produced maximum responding was higher in cadmium-exposed than control animals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparing self-reported cocaine use with repeated urine tests in outpatient cocaine abusers.

Sixty-one participants in outpatient therapy for cocaine dependence provided urine samples and self-reports of cocaine use 3 times a week for 4 weeks. Participants later gave a retrospective self-report of cocaine use for the month on the Addiction Severity Index (ASI). Comparisons with urine test values revealed substantial underreporting of cocaine use on both measures, and results from the 2 forms of self-report were only imperfectly correlated. More participants admitted to at least 1 cocaine use episode on the ASI than on the repeated self-reports, but the repeated reports provided a more accurate index of the relative frequency of cocaine use during the month. Self-reports can enhance cocaine use detection when urines are infrequently collected and can help determine whether consecutive positive urine samples represent elevated metabolite levels from a single drug use episode. However, self-reports cannot substitute for regular urine sampling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An ecological view of cigarette smoking.

Considers the social, biological, and physical inputs, mediating systems, and behavioral outputs of smoking in an ecological model. Implications of this model in understanding changes in smoking patterns are discussed. Experimental data is presented in an analysis of some determinants of the decision to stop smoking. Findings indicate that the individual stops smoking, not out of fear of consequences (e.g., lung cancer), but because of expectations of benefits: the decision to stop is based on subjectively expected utility. Attempts to change utilities have been inconclusive but do tend to indicate the importance of smoking patterns and that, for many individuals, smoking is an important source of ego strength. It is suggested that within Western society cigarettes are a major source for the fulfillment of the dominant values of achieving and doing. The need to change the society's as well as the individual's view of the utility of smoking is discussed. (27 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in mesenteric microcirculation in rats following repeated skin burns

Acute experiments were conducted on rats; repeated extensive burn of a convalescent who formerly sustained the burn disease was better tolerated, led tono fatal outcome and was accompanied by moderate microcirculatory disturbances. The smae burn was accompanied in intact rats by a severe shock followed by death, intravascular aggregation of erythrocytes and significant microcirculatory disturbances leading to disturbance of tissue nutrition. It is supposed that the results obtained could serve as an indirect proof that toxemia played an important role in the genesis of intravascular aggregation of erythrocytes in burn shock.     

Effects of serotonergic manipulations on cocaine self-administration in rats

Rats were trained to self-administer cocaine (0.5 mg/kg/infusion) and were then pretreated with the 5-HT1A agonist 8-OH-DPAT (0.125, 0.25 or 0.5 mg/kg, SC). 8-OH-DPAT pretreatment produced a decrease in reinforced response rates. When the effect of 8-OH-DPAT (0.5 mg/kg, SC) on responding for a range of cocaine doses was assessed, the drug produced a decrease in response rates when lower doses of cocaine served as the reinforcer. Fluoxetine (10 mg/kg, IV), an indirect 5-HT agonist, also reduced reinforced response rates for a low dose infusion of cocaine. Rates of responding for infusions of higher cocaine doses were not affected by fluoxetine pretreatment during an FR1 schedule of reinforcement. When an FR10 schedule of reinforcement was imposed, reinforced response rates for infusions of higher doses of cocaine were also reduced. Thus, under conditions that produce high rates of responding (low dose infusion or high ratio requirements for an infusion) fluoxetine reduced responding. This effect may be due to the effects at the 5-HT1A receptor, since 8-OH-DPAT produced a similar effect on cocaine self-administration. Given that the effects of these 5-HT agonists are observed only when low doses of cocaine serve as the reinforcer or when task demands are high, it is possible that the suppression of responding reflects an effect that is not specific to the reinforcing impact of cocaine. An alternative explanation for these effects incorporates a concept of unit cost/cocaine infusion that allows for direct comparison across studies that employ different reinforcement schedules.     

Oral cocaine self-administration in rhesus monkeys: Strategies for engendering reinforcing effects.

Orally delivered cocaine was established as a reinforcer for 8 rhesus monkeys (Macaca mulatta). Initially, each monkey was given a choice between the water vehicle and a 0.2 mg/ml cocaine concentration. The 0.2 mg/ml solution was not consumed in preference to water. One or more acquisition procedures were used with each monkey to establish orally delivered cocaine as a reinforcer. A common feature of all but one procedure was environmental situations that lead to the elective drinking of the cocaine solution. Evidence confirming the establishment of cocaine's reinforcing effects was obtained by testing each monkey across a broad range of cocaine concentrations under conditions of concurrent access to the cocaine solution and vehicle. Over a range of concentrations, the monkeys obtained greater cocaine than vehicle deliveries. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Phentermine/fenfluramine decreases cocaine self-administration in rhesus monkeys

Dopaminergic agonists can decrease cocaine self-administration at doses that do not decrease food-maintained responding, a pre-clinical effect indicative of a potential treatment for human cocaine abuse. To assess whether similar effects could be obtained with medications currently used to treat substance abuse, phentermine and fenfluramine were given alone and in combination to rhesus monkeys responding under schedules of food and cocaine delivery. Phentermine decreased cocaine-maintained responding with no effect on food-maintained responding. Fenfluramine also selectively decreased cocaine-maintained responding, but only at the highest dose. Combining a lower dose of fenfluramine with phentermine selectively decreased cocaine-maintained responding, but not more than with phentermine alone. These results suggest that phentermine, as well as its combination with fenfluramine, may be useful in the treatment of cocaine abuse.     

A genetic association for cigarette smoking behavior.

Dopaminergic genes are likely candidates for heritable influences on cigarette smoking. In an accompanying article, Lerman et al. (1999) report associations between allele 9 of a dopamine transporter gene polymorphism (SLC6A3-9) and lack of smoking, late initiation of smoking, and length of quitting attempts. The present investigation extended their study by examining both smoking behavior and personality traits in a diverse population of nonsmokers, current smokers, and former smokers (N?=?1,107). A significant association between SLC6A3-9 and smoking status was confirmed and was due to an effect on cessation rather than initiation. The SLC6A3-9 polymorphism was also associated with low scores for novelty seeking, which was the most significant personality correlate of smoking cessation. It is hypothesized that individuals carrying the SLC6A3-9 polymorphism have altered dopamine transmission, which reduces their need for novelty and reward by external stimuli, including cigarettes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strain differences in patterns of drug-intake during prolonged access to cocaine self-administration.

The current study examined possible interactions between genetic factors and prolonged drug access by testing the Fischer (F344), Lewis (LEW), and Wistar rat strains in a prolonged access cocaine self-administration (SA) procedure. Before prolonged access, the strains did not differ in breakpoints for food or cocaine with progressive ratio (PR) testing. The LEW and Wistar rats acquired cocaine SA faster than the F344s. With prolonged access to cocaine SA, the LEW and Wistar rats showed comparable within-session patterns that were higher at the outset of each session and decreased to a stable baseline. Alternatively, the F344 rats began sessions with lower intake and increased their rate of intake during the session. The F344 and Wistar rats took more drug per session than the LEW rats but did not differ from each other. Following prolonged access, the strains did not differ in breakpoints for food, but the Wistar rats had higher breakpoints for cocaine than the F344 rats. Possible underpinnings for the observed strain differences are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Abnormal mucosal glycoprotein synthesis in inflammatory bowel diseases is not related to cigarette smoking

Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn's disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn's disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 +/- (SD) 7.1 dpm/microgram biopsy protein, incorporation was increased in patients with active Crohn's disease (mean 41.2 +/- (SD) 10.4 dpm/microgram biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 +/- 7.8 dpm/microgram biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 +/- 13.8 dpm/microgram biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n = 58, mean 31.0 +/- (SD) 7.52 dpm/microgram biopsy protein; smokers, n = 27, mean 31.8 +/- (SD) 6.1 dpm/microgram biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn's disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related to cigarette smoking.     

Self-monitoring and reactivity in the modification of cigarette smoking.

The reactive effects of self-monitoring (SM) as a function of varying the specific nature of the target behavior and the perceived negative consequences of the behavior were investigated with 40 20–55 yr old chronic smokers (at least 15 cigarettes/day for 2 yrs). Ss were assigned to 1 of 4 conditions from stratified blocks based on initial smoking rates: (a) SM nicotine plus health hazard information; (b) SM nicotine with no health hazard information; (c) SM cigarettes plus health information; and (d) SM cigarettes with no health information. Ss self-monitored during a 4-wk nondemand phase and during a 4-wk treatment phase or until they quit smoking. The 2 nicotine SM groups showed greater reactivity. There were no differences among groups as a function of exposure to health hazard information. Results are discussed in relation to models of self-control and previous investigations of other parameters of reactive SM. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Smoked cocaine self-administration in females and voucher incentives for abstinence

Although some individuals are able to cope well with the challenges posed by HIV and AIDS, others experience psychological difficulties. This article reviews factors that facilitate or hinder successful coping with HIV including preexisting psychological functioning, medical health status, quality and adequacy of social support, stress-and-coping style, and perceived expected benefits of treatment. The article reviews studies evaluating the effects of group psychotherapy intervention for persons living with HIV. The article then describes clinical issues encountered in therapy groups for persons with HIV. These clinical issues include the presence of coexisting problems unrelated to HIV/AIDS, disclosure of HIV-positive serostatus to others, making changes in transmission-risk-behavior practices, AIDS-related bereavement and caregiving stress, establishing social supports, adhering to medical care regimens, and developing a positive self-identity as a person living with HIV. Practical considerations of group therapy for HIV-positive clients are also described.     

Locomotion and self-administration induced by cocaine in 129/OlaHsd mice lacking galanin.

Previous studies have demonstrated that the galanin system modulates responses to drugs of abuse such as morphine. The current study examined whether genetic deletion of galanin could affect the locomotor and reinforcing effects of cocaine in mice. We analyzed spontaneous motor activity and cocaine-induced hyperactivity in wild-type (GAL-WT) and knockout mice lacking galanin (GAL-KO) maintained on the 129/OlaHsd background. Our results indicate that cocaine enhanced locomotion (defined as moving more than 5 cm) dose-dependently in GAL-WT and GAL-KO mice. However, general activity (total beam breaks) was increased by cocaine only in GAL-WT mice. An additional experiment indicated that galnon, a nonselective galanin receptor agonist, did not affect cocaine-induced hyperactivity. In a second set of experiments, mice of both genotypes were trained to self-administer cocaine under a fixed ratio schedule, tested with various doses of cocaine and under different schedules of reinforcement. This set of experiments showed that cocaine self-administration did not differ markedly between genotypes. However, while GAL-WT mice acquired cocaine self-administration, a median split analysis showed that mice could be divided into large and small drug takers, whereas all GAL-KO mice behaved as small drug takers. Our results indicate that wild-type and galanin knockout mice on a congenic 129/OlaHsd background are responsive to the locomotor effects of cocaine and can acquire intravenous cocaine self-administration. However, the phenotype observed in GAL-KO mice does not support a major role for galanin in cocaine-induced hyperlocomotion and self-administration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of intravenous cocaine self-administration with concurrent access to food in cynomolgus monkeys.

The present study used a concurrent schedule of food and drug delivery in socially housed male cynomolgus monkeys (Macaca fascicularis; N?=?15) to study variables that influence cocaine acquisition. Each monkey was implanted with subcutaneous vascular access ports, and responding was maintained under a concurrent food, saline schedule with the lever associated with each stimulus presentation varied daily. Next, increasing cocaine doses (0.003–0.3 mg/kg/inj) were concurrently available with food for at least 5 consecutive sessions per dose. Under these conditions, an unexpected lever bias emerged in all 15 monkeys. The development of the lever bias could not be predicted on the basis of cocaine dose or total intake and was not related to social rank. These findings suggest that in monkeys, concurrent fixed-ratio schedules of food and cocaine presentation may result in persistent biased responding that overshadows cocaine preference in studies of acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The natural history of cigarette smoking: Predicting young-adult smoking outcomes from adolescent smoking patterns.

Assessed the magnitude of risk that adolescent cigarette smoking carries for adult smoking, using longitudinal data from 4,156 Ss surveyed originally during Grades 6–12 and followed up after completion of high school. Even infrequent experimentation (i.e., smoking only a few cigarettes) in adolescence significantly raised the risk for adult smoking by a factor of 16 compared to nonsmoking adolescents. Relative risk was also increased by early onset of smoking and by a stable, uninterrupted course from experimentation to regular smoking. Data support the importance of primary prevention programs directed at adolescent populations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)