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Results for “Behavior, Addictive”

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PubMed2006

Smoking as a decision among pregnant and non-pregnant women.

OBJECTIVES: The purpose was to examine values and beliefs related to smoking, and to test the validity of a decision model based on the product of the value of smoking-related events and states, and the belief that these will occur, (in decision research labeled Expected Utility, or EU). METHODS: Over a two-week period eighty women, divided into subgroups consisting of pregnant vs. non-pregnant women, and those intending vs. those not intending to quit smoking, performed evaluations of values and beliefs for the two conditions of quitting and not quitting smoking. RESULTS: For both pregnant and non-pregnant women expected utility of smoking was negative. Of all the four groups pregnant women not intending to quit smoking estimated the expected utility of smoking as least negative. CONCLUSIONS: A decision analytic approach is applicable to describe the addictive behavior of smoking. Values as well as beliefs about smoking should be stressed in smoking cessation programs, especially among pregnant women.

Adult↗

PubMed2006

Explicit and implicit alcohol-related cognitions and the prediction of future drinking in adolescents.

Both implicit and explicit alcohol-related cognitions might play a role in the early development of addictive behaviors. In this study, the association between both current and prospective alcohol use and implicit and explicit alcohol-related cognitions were measured in two different adolescent age groups (N=100; 51 twelve year olds, 49 fifteen year olds). Alcohol-related cognitions were measured on two dimensions (valence and arousal). A new measure, the unipolar Single Target Implicit Association Test (ST-IAT), was used as the implicit measure. A unipolar expectancy questionnaire was used as the explicit measure. Current alcohol use and alcohol use after one year were measured with an alcohol use questionnaire. Abstainers and drinkers differed in both their explicit and implicit alcohol-related cognitions moderated by age and gender. Additionally, a hierarchical regression analysis showed that implicit associations with alcohol added significantly to the prediction of prospective binge drinking, when controlling for grade, gender and explicit alcohol expectancies These results indicate the importance of taking implicit alcohol-related cognitions into account when intervention methods are developed.

Adolescent↗

PubMed2006

Smoking expectancies in smokers and never smokers: an examination of the smoking Consequences Questionnaire-Spanish.

The factor structure of smoking expectancies was examined in daily smokers and never smokers. Participants completed the Smoking Consequences Questionnaire-Spanish (SCQ-Spanish; [Cepeda-Benito, A., & Reig-Ferrer, A. (2000). Smoking consequences questionnaire-Spanish. Psychology of Addictive Behaviors, 14, 219-230.]). Using confirmatory factor analysis (CFA), the eight-factor structure of the SCQ-Spanish was replicated in smokers only. Except for beliefs about negative-health outcome expectancies, daily smoking rate was strongly associated with all types of smoking outcome expectancies. In comparison to men, women smokers reported greater weight control and negative-affect reduction consequences from smoking. An exploratory factor analysis (EFA) suggested a four-factor structure for the scores of never smokers. The findings represent not only the first cross-validation of the SCQ-Spanish but they were also congruent with the notion that first-hand smoking experience is not necessary for the development of multifaceted smoking expectancies. Nonetheless, the finding of a more complex factors structure in smokers than in never smokers is in line with the hypothesis that drug-use expectancies become more complex with drug-use experience.

Adult↗

PubMed2006

Volume and dose effects of experimenter-administered ethanol preloads on ethanol seeking and self-administration.

The present experiment used a behavioral model developed to separate the initial behavior required to obtain access to ethanol (appetitive responding or lever presses) from the actual self-administration (consummatory responding or intake) to test the hypothesis that these responses are under the control of different behavioral/physiological processes, and therefore differentially affected by an ethanol priming dose. In male, Long Evans rats, "preload" volume (0.5 and 2.0ml) and dose (approximately 10%, 25%, and 50% of the total normally consumed in nontreatment sessions translating to 0.1, 0.25, and 0.5g/kg) of ethanol were varied and administered by the experimenter via oral gavage prior to an operant session. Overall, there were no priming effects, or increases, in ethanol-reinforced responding resulting from the ethanol preloads. The findings showed that the low preload volume produced linear, dose-dependent decreases in both intake and seeking. However, while the high volume also produced a linear dose-dependent decrease in ethanol seeking, there was a decrease in intake at every dose. That is, ethanol seeking was insensitive to preload volume, while intake was affected in a dose-dependent manner except at the lowest dose when preload volume did play a role in intake regulation. These findings indicate that "fullness" and pharmacological cues differentially impact the appetitive and consummatory behaviors reinforced by ethanol solutions, with intake being more sensitive to preload volume and seeking being more sensitive to preload pharmacology.

Alcohol Drinking↗

PubMed2005

Suppression of conditioned nicotine and sucrose seeking by the cannabinoid-1 receptor antagonist SR141716A.

The present study shows that the selective cannabinoid CB1 receptor antagonist SR141716A attenuated responding for both nicotine- and sucrose-associated stimuli in a long-term extinction-reinstatement model. The results suggest that endocannabinoids play a general role in modulating cue reactivity or conditioned reinforcement following prolonged abstinence of both drug and natural reinforcers. In line with previous preclinical and recent clinical observations, our results provide a strong rationale for the use of CB1 antagonists in the treatment of addictive behaviors.

Animals↗

PubMed2006

Potentiation of cue-induced reinstatement of cocaine-seeking in rats by the anxiogenic drug yohimbine.

Stress and drug-associated cues can trigger drug desire and relapse in abstinent cocaine users. Although the role of these two factors in relapse is well documented, it remains unclear as to whether an interaction between stress and drug-associated cues can lead to an enhancement in cocaine-seeking behavior. Here, we assessed the effects of the anxiogenic alpha2-noradrenergic receptor antagonist, yohimbine, on reinstatement of cocaine-seeking in rats either in the presence or absence of cocaine-associated cues. Yohimbine pretreatment in the absence of cocaine-associated cues or cues by themselves reliably reinstated responding on the previously cocaine-paired lever (3-4 times higher than extinction levels). However, animals showed greatly potentiated responding if yohimbine preceded cue-induced reinstatement (10-13 times higher than extinction levels, or 3-5 times over cues or yohimbine alone). While cocaine self-administration produced a significant increase in plasma corticosterone, plasma corticosterone levels did not show a clear relationship to cocaine-paired lever responding during cue and/or yohimbine-induced reinstatement. These results demonstrate that exposure to drug-paired cues during a stressful state can greatly potentiate cocaine-seeking and suggest that future treatment interventions should target multiple modalities.

Analysis of Variance↗

PubMed2006

Analysis of alcohol-related phenotypes in F2 progeny derived from FH/Wjd and ACI/N rat strains reveals independent measures and sex differences.

Ethanol associated addictive behaviors are governed by a combination of multiple gene action (polygenic or quantitative trait) and environmental factors. We produced F2 progeny from F1 crosses derived from the alcohol-preferring Fawn-Hooded (FH/Wjd) rat strain and the alcohol-nonpreferring ACI/N strain. We compared different phenotypes related to alcohol intake in more than 600 F2 progeny. We found that female rats had significantly higher mean voluntary and forced ethanol, water, saccharin and total fluid intakes than male rats. Therefore, we compared these measures in the top 15th percentile with those in bottom 15th percentile of the F2 total ethanol intake distribution separately for males and females. The two tail comparison of means showed that only the trait of alcohol preference differed significantly in both males and females, suggesting that alcohol preference is closely related to alcohol intake. Because of the detailed information about the F1 parents of the F2 progeny, it was possible to determine parental effects. For swim test immobility, for example, the F2 progeny derived from FA(m)/FA(f) parents (ACI maternal inheritance) had the lowest mean value of 130s while the F2 progeny from AF/AF parents (FH maternal inheritance) had the highest mean value of 157s (p<0.005). The F2 progeny derived from FA/AF parents (FH maternal inheritance) showed higher mean values of forced alcohol intake than FA/FA parents (FH paternal inheritance) (6.58 and 6.36g/kg/day, respectively) suggesting that the FH mother had a significantly (p<0.0001) greater effect on forced alcohol intake than the FH father. It is concluded from these analyses that alcohol-related phenotypes are segregating independently and may be influenced by maternal and sex factors.

Alcohol Drinking↗

PubMed2004

The anxiogenic drug yohimbine reinstates methamphetamine seeking in a rat model of drug relapse.

BACKGROUND: Brain noradrenaline is involved in footshock stress-induced reinstatement of drug seeking in a rat relapse model. We studied whether yohimbine, an alpha-2 adrenoceptor antagonist that increases noradrenaline release and induces anxiety-like responses in human and nonhuman subjects, would reinstate methamphetamine seeking in rats. METHODS: In experiment 1, the effect of yohimbine (1.25-2.5 mg/kg) on reinstatement was compared with that of intermittent footshock (5 min;.2-.6 mA) in rats that were trained to lever press for intravenous methamphetamine (9-11 days) and subsequently underwent 7 days of extinction training. In experiment 2, the effect of yohimbine on reinstatement of drug seeking was determined during early (1 day) and late (21 or 51 days) withdrawal periods. On the test days, rats were first given 3-hour extinction sessions and were then tested for reinstatement induced by yohimbine. RESULTS: In experiment 1, both yohimbine and footshock stress reinstated methamphetamine seeking after extinction. In experiment 2, extinction responding was higher after 21 or 51 withdrawal days than after 1 withdrawal day. In contrast, no significant time-dependent changes in yohimbine-induced reinstatement were observed. CONCLUSIONS: Results indicate that yohimbine is a potent stimulus for reinstatement of methamphetamine seeking in a rat relapse model.

Adrenergic alpha-Antagonists↗

PubMed2006

Distinct patterns of neural activation associated with ethanol seeking: effects of naltrexone.

BACKGROUND: Alcoholism, like other substance abuse disorders, is a chronically relapsing condition. Compared with other abused drugs, however, little is known about the neural mechanisms mediating ethanol (EtOH)-craving and -seeking behavior leading to relapse. This study, therefore, was conducted to identify candidate brain regions that are recruited by an EtOH-associated contextual stimulus (S(+)). A secondary objective was to determine whether EtOH S(+)-elicited neural recruitment patterns are modified by the opiate antagonist naltrexone (NTX), a compound that reduces cue-induced craving in alcoholics and attenuates ethanol seeking in animal models of relapse. METHODS: Rats were tested in a conditioned reinstatement model of relapse with subsequent examination of brain c-fos expression patterns elicited by an EtOH S(+) versus a cue associated with nonreward (S(-)). In addition, modification of these expression patterns by NTX was examined. RESULTS: The EtOH S(+) reinstated extinguished responding and increased c-fos expression within the prefrontal cortex, hippocampus, nucleus accumbens, and hypothalamic paraventricular nucleus (PVN). Naltrexone suppressed the S(+)-induced reinstatement and attenuated hippocampal CA3 c-fos expression, while increasing neural activity in the extended amygdala and PVN. CONCLUSIONS: Ethanol-associated contextual stimuli recruit key brain regions that regulate associative learning, goal-directed behavior, and Pavlovian conditioning of emotional significance to previously neutral stimuli. In addition, the data implicate the hippocampus, amygdala, and PVN as potential substrates for the inhibitory effects of NTX on conditioned reinstatement.

Alcohol Drinking↗

PubMed2005

Clorazepate affects cell surface regulation of delta and kappa opioid receptors, thereby altering buprenorphine-induced adaptation in the rat brain.

Concomitant abuse of buprenorphine (BPN) and benzodiazepines (BZD) may relate to a pharmacodynamic interaction between the two. The objective of the present work was to investigate the acute and chronic effects of clorazepate (CRZ) alone or in combination with BPN on selective kappa opiate tritiated ligand [3H]-U69 593 and delta opiate radioligand [3H]-deltorphine II binding in the rat brain. Bmax (maximal receptor density) and Kd (the dissociation constant) were directly determined at different brain regions of interest (ROI) selected for high densities of kappa and/or delta receptors in rats treated with BPN and/or CRZ. The agents were administered either once or for 21 consecutive days. Differences in Bmax and Kd (for both specific ligands) were related to drug treatment and receptor location. Globally, single BPN administration induced no changes in kappa or delta opiate receptor binding, whereas repeated BPN administration up-regulated kappa receptor density and decreased delta affinity. At the kappa receptor level, repeated administration of CRZ acted only on Kd, whereas the delta receptor was up-regulated. Repeated addition of CRZ to BPN had no effect on kappa receptor Bmax versus chronic controls. By significantly decreasing Bmax, CRZ nullified the effect of chronic BPN on the kappa receptor. The modifications were strongest in the nucleus accumbens, where both types of receptor occur. Treatments had region-selective effects in some brain areas, such as the amygdala, periaqueductal gray matter, hypothalamus and caudate putamen. Increased mu and delta receptor densities would be expected to provide reinforcement by enhancing reward, and impairment of kappa receptor availability would be expected to decrease aversion. The effects described are likely to influence addictive behavior among people abusing BZD and BPN.

Adaptation, Physiological↗

PubMed2006

Subadditive withdrawal from cocaine/kappa-opioid agonist combinations in Planaria.

We have previously developed and extensively characterized a convenient and sensitive metric for the quantification of withdrawal responses using Planaria. Planaria are particularly valuable for these studies because of their permeable exteriors and their relevant neurotransmitter systems (e.g., dopaminergic, opioid, and serotonergic). In the present study, we used this metric and mathematically rigorous joint-action analysis to investigate poly-drug withdrawal from fixed-ratio cocaine/kappa-opioid agonist combinations. The D50 (concentration producing half-maximal effect) for cocaine and U-50,488H was 10.3 and 1.02 microg, respectively. The D50 for 19:1 or 1:19 combinations did not differ significantly (p>0.05) from expected additive values (11.6+/-3.0 vs. 9.9+/-1.4 and 1.1+/-0.2 vs. 1.5+/-0.1, respectively), but the 3:1, 1:1, and 1:3 ratios did (34.5+/-6.9 vs. 7.7+/-1.1; 55.1+/-10.0 vs. 5.7+/-0.7; and 40.8+/-8.9 vs. 3.3+/-0.4, respectively), indicating subadditive interaction at these ratios. The finding of subadditivity in this model suggests that abstinence-induced withdrawal from the combination is less intense than that predicted from the individual drug potencies. The concept that certain combinations of drugs leads to attenuated withdrawal might generalize to humans.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2004

The endocannabinoid-CB(1) receptor system in pre- and postnatal life.

Recent research suggests that the endogenous cannabinoids ("endocannabinoids") and their cannabinoid receptors have a major influence during pre- and postnatal development. First, high levels of the endocannaboid anandamide and cannabinoid receptors are present in the preimplantation embryo and in the uterus, while a temporary reduction of anandamide levels is essential for embryonal implantation. In women accordingly, an inverse association has been reported between fatty acid amide hydrolase (the anandamide degrading enzyme) in human lymphocytes and miscarriage. Second, CB(1) receptors display a transient presence in white matter areas of the pre- and postnatal nervous system, suggesting a role for CB(1) receptors in brain development. Third, endocannabinoids have been detected in maternal milk and activation of CB(1) receptors appears to be critical for milk sucking by newborn mice, apparently activating oral-motor musculature. Fourth, anandamide has neuroprotectant properties in the developing postnatal brain. Finally, prenatal exposure to the active constituent of marihuana (Delta(9)-tetrahydrocannabinol) or to anandamide affects prefrontal cortical functions, memory and motor and addictive behaviors, suggesting a role for the endocannabinoid CB(1) receptor system in the brain structures which control these functions. Further observations suggest that children may be less prone to psychoactive side effects of Delta(9)-tetrahydrocannabinol or endocannabinoids than adults. The medical implications of these novel developments are far reaching and suggest a promising future for cannabinoids in pediatric medicine for conditions including "non-organic failure-to-thrive" and cystic fibrosis.

Animals↗

PubMed2004

The NK(1) receptor antagonist WIN51708 reduces sensitization after chronic cocaine.

We tested the tachykinin NK(1) receptor antagonist WIN51708 (17betahydroxy17alphaethynyl5alphaandrostanol[3,2b]pyrimido[1,2-a]benzimidazole) in a behavioral sensitization model. Rats were given 7 days of cocaine then 7 days of withdrawal to induce sensitization. Thereafter, another 7 days of cocaine with WIN51708 (2 mg/kg i.p.) given 3.5 h after each cocaine injection was given. WIN51708 reversed sensitization but had no effect on controls. NK(1) receptor antagonists may have use in stimulant abuse and schizophrenia treatment.

Androstanes↗

PubMed2005

The serotonin/noradrenaline reuptake inhibitor venlafaxine attenuates acquisition, but not maintenance, of intravenous self-administration of heroin in rats.

Opioids and antidepressants are frequently used for the treatment of various pain conditions. A combination of both drug classes may be more effective than either treatment alone, and combined treatment with an antidepressant may result in an opiate-sparing effect. Although it has been shown that antidepressants can attenuate self-administration of psychomotor stimulant and depressant drugs, it is not known whether they also attenuate self-administration of opiates. To determine whether venlafaxine, a serotonin/noradrenaline reuptake inhibitor with antidepressive and analgesic properties, affects acquisition and maintenance of intravenous heroin self-administration in rats, male Long-Evans rats were trained to press a lever in order to receive heroin (0.05 mg/kg/infusion) under a fixed ratio or a progressive ratio schedule. A control group was trained in a fixed ratio food-reinforced operant procedure. The effect of venlafaxine on operant responding for heroin and food was assessed both during acquisition and, in separate groups of rats, during maintenance (i.e., after acquisition) of self-administration behaviour. Daily treatment with venlafaxine (10 mg/kg i.p.) before the operant session attenuated the acquisition of responding for heroin, but not for food. However, when tested during the maintenance phase in rats showing stable responding, acute treatment with venlafaxine only marginally affected operant responding for heroin under a fixed ratio:10 schedule of reinforcement, and neither acute nor subchronic (once daily during 4 weeks) venlafaxine treatment affected responding under a progressive ratio schedule. Thus, daily treatment with an antidepressant attenuates the acquisition of heroin self-administration in a behaviourally specific manner, while having only marginal effects on maintenance of heroin self-administration.

Animals↗

PubMed2005

Suppression of alcohol self-administration and cue-induced reinstatement of alcohol seeking by the mGlu2/3 receptor agonist LY379268 and the mGlu8 receptor agonist (S)-3,4-DCPG.

Glutamatergic neurotransmission has been suggested to modulate cue-induced drug-seeking behavior. Here we examined the effects of metabotropic glutamate receptor agonists on alcohol self-administration and cue-induced reinstatement. Rats were trained to self-administer 10% w/v ethanol under an FR1 schedule of reinforcement during 30-min sessions. In the reinstatement experiments, ethanol and a non-rewarding quinine solution (available on alternating days) were paired with olfactory stimuli (S+/S-) as well as light (CS+) or tone (CS-) stimuli. Following extinction training, reinstatement of responding was induced by the ethanol-associated stimuli (S+/CS+). The mGlu2/3 receptor agonist LY379268 (0, 1, 3 and 5 mg/kg i.p.) and the mGlu8 receptor agonist (S)-3,4-DCPG (0, 5, 10 and 15 mg/kg i.p.) attenuated alcohol self-administration and reinstatement at doses that decreased also spontaneous locomotor activity. The results suggest that metabotropic glutamate receptors may have a role in the modulation of alcohol seeking and self-administration. However, further studies with ligands with fewer motor-suppressant side effects are needed.

Alcohol Drinking↗

PubMed2004

Comorbid psychiatric diagnoses in kleptomania and pathological gambling: a preliminary comparison study.

Kleptomania and pathological gambling (PG) are currently classified in the DSM IV as impulse control disorders. Impulse control disorders are characterized by an overwhelming temptation to perform an act that is harmful to the person or others. The patient usually feels a sense of tension before committing the act and then experiences pleasure or relief while in the process of performing the act. Kleptomania and PG are often associated with other comorbid psychiatric diagnoses. Forty-four pathological gamblers and 19 kleptomanics were included in this study. All enrolled patients underwent a complete diagnostic psychiatric evaluation and were examined for symptoms of depression and anxiety using the Hamilton depression rating scale and the Hamilton anxiety rating scale, respectively. In addition, the patients completed self-report questionnaires about their demographic status and addictive behavior. The comorbid lifetime diagnoses found at a high prevalence among our kleptomanic patients included 47% with affective disorders (9/19) and 37% with anxiety disorders (7/19). The comorbid lifetime diagnoses found at a high prevalence in our sample of pathological gamblers included 27% with affective disorders (12/44), 21% with alcohol abuse (9/44), and 7% with a history of substance abuse (3/44). A larger study is needed to confirm these preliminary results.

Adult↗

PubMed2005

Attenuated cortisol response to alcohol in heavy social drinkers.

Individual differences in response to stress may play a role in the development and maintenance of addictive behaviors. While there is evidence that people with a biological family history for alcoholism have a blunted cortisol response to alcohol, data are lacking in other at-risk subgroups, such as heavy social drinkers. The present study examined salivary cortisol response to administration of 0.0, 0.4 (2 drink equivalent), and 0.8 g/kg (4 drink equivalent) alcohol in two groups of social drinkers: heavy drinkers (n=32) and light social drinkers (n=23). The study was conducted double-blind and drink-order was counterbalanced between groups. Salivary cortisol and subjective measures were obtained at predrink baseline, and 15, 45, 105, and 165 min after beverage consumption. Results showed a significant groupxdosextime interaction (p<0.005), with alcohol (0.8 g/kg) producing an attenuated cortisol response in heavy drinkers compared to the light drinkers during the declining phase of the BAC. This outcome remained even after controlling for the effects of smoking status, family history of alcoholism, sex, and negative affect ratings during the session. Neither placebo nor the lower dose of alcohol significantly increased cortisol levels. In sum, a relatively high dose of alcohol produced a smaller increase in cortisol in heavy drinkers compared to light drinkers. The reduced cortisol reactivity in the heavier drinkers is consistent with reports that individuals at risk for alcoholism are hyporesponsive to physical and psychological stress. Further research may help determine whether alteration in cortisol response to alcohol is a biological marker of the propensity to abuse alcohol.

Adult↗

PubMed2004

Reduction of withdrawal signs after chronic nicotine exposure of alpha-calcitonin gene-related peptide knock-out mice.

Nicotine, the main substance responsible for the addictive behavior of smokers, binds to a variety of nicotinic acetylcholine receptors (nAChRs) diversely distributed in the brain, notably in areas involved in motivation and reward mechanisms. The alpha-calcitonin gene-related peptide (alphaCGRP) has been previously shown to modulate the functions of nAChRs and is released in brain areas implicated in motivation, such as the amygdala or the ventral tegmental area. Interestingly, alphaCGRP -/- mice display a decrease in morphine withdrawal symptoms. In this context, we investigate the tolerance and withdrawal symptoms in alphaCGRP -/- mice exposed to acute and chronic nicotine. We report that these animals develop a normal tolerance to the antinociceptive effects of nicotine, but display an attenuation of somatic withdrawal symptoms.

Animals↗