PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Behavior, Addictive”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed2006

Environmental cues, alcohol seeking, and consumption in baboons: effects of response requirement and duration of alcohol abstinence.

BACKGROUND: Environmental stimuli (cues) that have been paired with alcohol drinking may evoke classically conditioned states that in turn influence alcohol consumption and relapse to heavy drinking. Animal models using chained schedules of alcohol reinforcement may be useful for examining such complex interactions. METHODS: Alcohol drinking was established in 4 baboons. A sequence of lights and tones was presented during daily 3-hour sessions. First, cues were presented alone and no programmed contingencies were in effect. Second, cues were paired with 3 linked components consisting of different behavioral contingencies leading to and concluding with access to alcohol for self-administration in the last component (i.e., a chained schedule of alcohol reinforcement). Third, the effects of withholding alcohol access (i.e., forced abstinence) and increasing the number of lever responses required per drink were evaluated. RESULTS: Cues paired with a chained schedule of alcohol reinforcement engendered behaviors that brought baboons into contact with alcohol-related cues and occasioned operant responding that facilitated access to alcohol (alcohol seeking) during components that preceded alcohol access. Increasing the response requirement for each drink decreased the number of drinks and volume of alcohol consumed, but did not alter alcohol seeking. On the first session after 14 days of alcohol abstinence, latency to complete the operant requirement that produced alcohol access was decreased while both alcohol self-administration and volume of alcohol consumed were increased. CONCLUSIONS: Alcohol self-administration and consumption were sensitive to increases in response requirement and duration of alcohol abstinence, while seeking was only enhanced by duration of alcohol abstinence. This animal model may be useful to further examine the interactions between environmental cues and behaviors associated with seeking and consumption of alcohol and to evaluate the efficacy of potential alcohol treatment drugs on these behaviors.

Alcohol Drinking↗
PubMed2005

Dopamine-mediated disinhibition in the CA1 region of rat hippocampus via D3 receptor activation.

The hippocampal formation is thought to contribute to both addictive behaviors and to psychotic disorders, and the actions of the neurotransmitter dopamine are intimately involved with these disease states. We have used both whole-cell and extracellular recording techniques in hippocampal slices to investigate the actions of both cocaine and dopamine receptor agonists in the CA1 region. In the presence of cocaine (10 microM), endogenously released dopamine decreased monosynaptic inhibitory postsynaptic currents (IPSCs) evoked from stratum radiatum but not from stratum oriens. This effect of cocaine was not blocked by the D(1/5) antagonist SCH 23390 ({R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine}) (3 microM), whereas several D(2)-like dopamine receptor antagonists prevented the cocaine-induced decrease in the IPSC. The most selective of the effective antagonists tested was the D(3) antagonist, U 99194 ({5,6-dimethoxy-indan-2-yl dipropylamine}) maleate (1 microM). An exogenously applied D(3)-selective dopamine receptor agonist, PD 128907 ({(+)-(4aR, 10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]-benzopyrano-[4,3-b]-1,4-oxazin-9-ol}) (1 microM), also significantly inhibited the IPSC, providing further evidence that the activation of the D(3) subtype of dopamine receptor by endogenously released dopamine can modulate inhibition in the CA1 region. This disinhibitory action on pyramidal cells also increased synaptic excitability following Schaffer collateral stimulation, as demonstrated by either a decrease in paired-pulse inhibition of the population spike response or by an increase in the excitatory component of the mixed synaptic response evoked from stratum radiatum. These actions indicate that the activation of D(3) receptors by endogenously released dopamine, especially under conditions of transporter blockade, may significantly impact the processing of synaptic information through the stratum radiatum layer of the hippocampus.

Animals↗
PubMed2006

Protein kinase A activation down-regulates, whereas extracellular signal-regulated kinase activation up-regulates sigma-1 receptors in B-104 cells: Implication for neuroplasticity.

The sigma-1 receptor (Sig-1R) can bind psychostimulants and was shown to be up-regulated in the brain of methamphetamine self-administering rats. Up-regulation of Sig-1Rs has been implicated in neuroplasticity. However, the mechanism(s) whereby Sig-1Rs are up-regulated by psychostimulants is unknown. Here, we employed a neuroblastoma cell line B-104, devoid of dopamine receptors and transporter, and examined the effects of psychostimulants as well as cAMP on the expression of Sig-1Rs in this cell line, with a specific goal to identify signal transduction pathway(s) that may regulate Sig-1R expression. Chronic treatments of B-104 cells with physiological concentrations of cocaine or methamphetamine failed to alter the expression of Sig-1Rs. N6,2'-O-Dibutyryl-cAMP (dB-cAMP), when used at 0.5 mM, caused a down-regulation of Sig-1Rs that could be blocked by a protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89). However, dB-cAMP, when used at 2 mM, caused an up-regulation of Sig-1Rs that was insensitive to the H-89 blockade but was partially blocked by an extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone). Furthermore, 2 mM dB-cAMP induced an ERK phosphorylation lasting at least 90 min, at which time the phosphorylation caused by 0.5 mM dB-cAMP had already diminished. PD98059, applied 90 min after addition of 2 mM dB-cAMP, attenuated the Sig-1R up-regulation. Our results indicate that cAMP is bimodal in regulating Sig-1R expression: a down-regulation via PKA and an up-regulation via ERK. Results also suggest that psychostimulants may manipulate the cAMP-PKA-Sig-1R and/or the cAMP-ERK-Sig-1R pathways to achieve a neuroplasticity that favors addictive behaviors.

Amino Acid Sequence↗
PubMed2004

The mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine decreases ethanol consumption via a protein kinase C epsilon-dependent mechanism.

Glutamatergic neurotransmission plays a critical role in addictive behaviors, and recent evidence indicates that genetic or pharmacological inactivation of the type 5 metabotropic glutamate receptor (mGluR5) reduces the self-administration of cocaine, nicotine, and alcohol. Because mGluR5 is coupled to activation of protein kinase C (PKC), and targeted deletion of the epsilon isoform (PKCepsilon) in mice reduces ethanol self-administration, we investigated whether there is a functional link between mGluR5 and PKCepsilon. Here, we show that acute administration of the mGluR5 agonist (R,S)-2-chloro-5-hydroxyphenylglycine to mice increases phosphorylation of PKCepsilon in its activation loop (T566) as well as in its C-terminal region (S729). Increases in phospho-PKCepsilon are dependent not only on mGluR5 stimulation but also on phosphatidylinositol-3 kinase (PI3K). In addition, the selective mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) reduced basal levels of phosphorylation of PKCepsilon at S729. We also show that MPEP dose dependently reduced ethanol consumption in wild-type but not in PKCepsilon-null mice, suggesting that PKCepsilon is an important signaling target for modulation of ethanol consumption by mGluR5 antagonists. Radioligand binding experiments using [(3)H]MPEP revealed that these genotypic differences in response to MPEP were not a result of altered mGluR5 levels or binding in PKCepsilon-null mice. Our data indicate that mGluR5 is coupled to PKCepsilon via a PI3K-dependent pathway and that PKCepsilon is required for the ability of the mGluR5 antagonist MPEP to reduce ethanol consumption.

Alcohol Drinking↗
PubMed2000

Subtype-selective inhibition of neuronal nicotinic acetylcholine receptors by cocaine is determined by the alpha4 and beta4 subunits.

Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels of the central and peripheral nervous system that regulate synaptic activity from both pre- and postsynaptic sites. Nicotine binding to brain nAChRs is thought to underlie the induction of behavioral addiction to nicotine, probably as a result of desensitizing/inhibitory effects. Here, another commonly abused drug, cocaine, is shown to selectively inhibit particular nAChR subtypes with a potency in the low micromolar range by interacting with separate sites associated with the alpha4 and beta4 nAChR subunits. Chimeric receptor subunits and site-directed mutants were used to localize sequence determinants of cocaine affinity to: 1) a region of alpha4 located between residues 128 and 267 and 2) a site within the pore-lining M2 domain of beta4 that includes the 13' phenylalanine residue. The voltage dependence for inhibition associated with each site is consistent with these results. Analysis of the effects of incorporation of mutant and chimeric subunits also permitted identification of sequence elements important in receptor activation. For alpha3-containing receptors, a region or regions contained within the N-terminal extracellular domain of neuronal beta subunits influence the time course of responses to acetylcholine. Conversely, the 13' residue of the beta4 subunit M2 region is important in determining acetylcholine potency, indicating a role for this residue in agonist binding/gating processes. In summary, the present work describes sequence elements critical in both cocaine inhibition and acetylcholine activation of nAChRs and indicates that nAChRs may provide a site of interaction for the effects of nicotine and cocaine in the nervous system.

Amino Acid Sequence↗
PubMed1999

Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice.

The function of the central cannabinoid receptor (CB1) was investigated by invalidating its gene. Mutant mice did not respond to cannabinoid drugs, demonstrating the exclusive role of the CB1 receptor in mediating analgesia, reinforcement, hypothermia, hypolocomotion, and hypotension. The acute effects of opiates were unaffected, but the reinforcing properties of morphine and the severity of the withdrawal syndrome were strongly reduced. These observations suggest that the CB1 receptor is involved in the motivational properties of opiates and in the development of physical dependence and extend the concept of an interconnected role of CB1 and opiate receptors in the brain areas mediating addictive behavior.

Analgesics, Opioid↗
PubMed2005

Economic causes and consequences of obesity.

Obesity is not only a health but also an economic phenomenon. This chapter (a) examines underlying economic causes, such as technological advancements, behind the obesity epidemic; (b) describes economic consequences of obesity, including increasing obesity-related medical expenditures; and (c) discusses the role of government in combating the obesity epidemic. Because of the high costs of obesity, and the fact that the majority of these costs are financed by taxpayers, there is a clear motivation for government to try to reduce these costs. However, because obesity may result from poor information and addictive behavior and/or as a result of living in an increasingly obesogenic environment, interventions will need to be multifaceted to ensure the best chance of success.

Attitude to Health↗
PubMedDate not supplied

Comorbidity of dependent personality disorder and separation anxiety disorder in addictive disorders and in healthy subjects.

The aim of the study was to determine the comorbidity of dependent personality disorder (DPD) and separation anxiety disorder (SAD) in large nonclinical and clinical samples. Using a cross-sectional method, the relationship between these disorders was studied in 784 healthy subjects and in 708 subjects presenting with various addictive behaviors. DPD was significantly associated with SAD in healthy subjects, alcoholics, drug abusers and anorectic and bulimic patients. The comorbidities of SAD and DPD suggest that specific therapeutic strategies could be discussed. Moreover, longitudinal studies are required to determine if SAD constitutes a risk factor for DPD.

Adolescent↗
PubMed1984

Withdrawal responses to abrupt discontinuation of desmethyldiazepam.

The authors present the results of a controlled observation of withdrawal reactions accompanying cessation of desmethyldiazepam (clorazepate) therapy. The two subjects studied had had generalized anxiety disorder for several years; both were free from manifestations of other forms of psychopathology or addictive behavior patterns. Both patients maintained stable patterns of clorazepate use at modest doses for extended periods of time. The findings suggest that the long plasma half-life of clorazepate does not offer unique protection from withdrawal reactions associated with long-term therapy. Manifestations of these withdrawal reactions are indistinguishable from reactions associated with other benzodiazepine compounds.

Acute Disease↗
PubMed1985

Prognostic indicators in the psychotherapy of borderline patients.

Although diagnostic and therapeutic difficulties, including countertransference problems, in borderline patients make prognostic estimates hazardous, practical necessity often requires a prognostic judgment regarding treatability. This paper proposes a list of prognostic indicators in borderline patients which may be useful to the psychotherapist in the evaluation of treatability. Unfavorable prognostic indicators include history of brutalized early environment, severe behavior problems in childhood, antisocial behavior, addictions, egosyntonicity, superficial or highly disturbed relationships, marked narcissistic features, injurious social environment; and, in the course of therapy, strong negative reaction of the therapist toward the patient, and antisocial acting out. Suggesting a more favorable prognosis for psychotherapy are: nonspecific personality traits which may promote the therapeutic relationship (likeableness, warmth, reliability, or interest in people), and intact sublimatory outlets (talents, skills). In general, the quality of object relations, especially the therapist-patient relationship, including the countertransference, is crucial to prognosis. The unfavorable prognostic implications of certain atypical forms of anxiety, depression, and dependency, as well as anhedonia and abulia, are discussed. Borderline patients with infantile features probably have better prognosis than is generally recognized; with narcissistic features, a worse prognosis than generally recognized.

Adult↗
PubMed1995

Gambling among adolescents.

Gambling onset during adolescence has been the subject of recent articles in the lay press. This study reports on the incidence of gambling in adolescents. There were 97 males (48.7%) and 102 females (51.3%) between the ages of 12 and 18 years. The mean age of the gamblers was 15.12 +/- 1.83 (SEM), and of the nongamblers 14.36 +/- 1.78. Eighty-three percent of the males and 61% of the females reported gambling. Forty-four percent of those who gambled, but only 26% of the nongamblers, reported having at least one parent who gambled. Our study confirms the high incidence of gambling by teenagers. Of concern is the potential link between gambling and other risk-taking or addictive behaviors. Perhaps we should include gambling as part of our anticipatory guidance for adolescents.

Adolescent↗
PubMed2006

Correlates of subjective stress among drug court clients.

Psychosocial stress is consistently found to promote initiation, intensification, and relapse in drug abuse. It would, therefore, be desirable to identify characteristics of offenders who are at heightened risk for stress-induced exacerbations of addictive behavior. In this cross-sectional, correlational, interview study, 500 clients of two Kentucky drug courts averaged 30 years of age and were predominantly male, White, employed, high school educated, single, and adjudicated in small- and medium-size cities. Five independent correlates of greater subjective stress emerged in stepwise multiple regression analysis (R2 = .395): use of escape-avoidance coping, positive reappraisal coping (inversely associated), more negative life events, better self-rated health (inversely associated), and access to social support related to work problems (inversely associated). Treatment interventions emphasizing effective coping styles and building of social support as well as managing of negative life events and perceptions of health may serve to lessen subjective stress and its consequences in drug-abusing criminal populations.

Adaptation, Psychological↗
PubMed2005

The epidemiology of college alcohol and gambling policies.

BACKGROUND: This article reports the first national assessment of patterns of drinking and gambling-related rulemaking on college campuses (e.g., punitive versus recovery oriented). Analyses relating school policies to known school rates of drinking or gambling identified potentially influential policies. These results can inform and encourage the development of guidelines, or "best practices," upon which schools can base future policy. METHODS: The college policy information was collected from handbooks, Web sites and supplemental materials of 119 scientifically selected colleges included in the fourth (2001) Harvard School of Public Health College Alcohol Study (CAS). A coding instrument of 40 items measured the scope and focus of school alcohol and gambling policies. This instrument included items to measure the presence of specific policies and establish whether the policies were punitive or rehabilitative. A total of 11 coders followed a process of information extraction, coding and arbitration used successfully in other published studies to codify policy information. RESULTS: Although all schools had a student alcohol use policy, only 26 schools (22%) had a gambling policy. Punitive and restrictive alcohol policies were most prevalent; recovery-oriented policies were present at fewer than 30% of schools. Certain alcohol and gambling policies had significant relationships with student binge drinking rates. CONCLUSIONS: The relative lack of college recovery-oriented policies suggests that schools might be overlooking the value of rehabilitative measures in reducing addictive behaviors among students. Since there are few college gambling-related policies, schools might be missing an opportunity to inform students about the dangers of excessive gambling.

Journal Article↗
PubMed1999

Management of patients with bipolar mood disorder and substance dependence.

UNLABELLED: Nine patients with bipolar mood disorder and concurrent substance dependence were treated in an 18-bed inpatient addiction unit over a 3-month period. A multidisciplinary team approach used a medicalized Minnesota model and stressed the establishment of a positive diagnosis and individualization of management strategies for each patient. Clinically significant affective symptoms that required acute psychiatric intervention developed in several patients during hospitalization. Manic symptoms developed in three patients during sedative withdrawal, requiring the team to differentiate manic symptoms from physiologic withdrawal; and two patients became severely depressed, requiring pharmacologic management and suicide-prevention strategies. SUMMARY: Our experience with the patients in this case series supports the contention that there is no simple, uniform approach to the substance-dependent patient with bipolar disorder. Treatment teams must be prepared to differentiate complex syndromes and to manage manic, depressive, and addictive behaviors.

Adult↗
PubMed2003

The role of the hypocretinergic system in the integration of networks that dictate the states of arousal.

Recent studies have led to the discovery of a neuropeptide system that regulates arousal states. The hypocretins (hcrt1 and hcrt2, also called the orexins) are neuropeptides of related sequence derived from the same precursor whose expression is restricted to a few thousand neurons of the lateral hypothalamus. Two G-protein-coupled receptors for the hypocretins have been identified, and these have different distributions within the central nervous system and differential affinities for the two hypocretins. Hypocretin fibers project throughout the brain, including several areas implicated in cardiovascular function and regulation of the sleep-wake cycle. Central administration of synthetic hypocretin-1 affects blood pressure, hormone secretion and locomotor activity, and increases wakefulness while suppressing rapid eye movement sleep. Most human patients with narcolepsy have greatly reduced levels of hypocretin peptides in their cerebral spinal fluid and no or barely detectable hypocretin neurons in their hypothalami, suggestive of autoimmune attack. Development of nonpeptidergic hypocretin antagonists may prove useful in sleep disorders, whereas hypocretin agonists may be used to treat narcolepsy and excessive daytime sleepiness. The hypocretins are also an excellent target for the pharmacological treatment of the deregulated arousal state that characterizes depression or addictive behavior.

Animals↗
PubMed1999

Oral leukoplakia status six weeks after cessation of smokeless tobacco use.

BACKGROUND: This study evaluated the prevalence and risk of developing oral leukoplakia in smokeless tobacco, or ST, users and the response of these leukoplakic lesions after six weeks of involuntary tobacco cessation. U.S. Air Force basic military training provided an environment of a mandatorily tobacco-free setting. METHODS: The authors designed their investigation as a case control study with a nested cohort study. The principal investigator (G.C.M.) conducted oral examinations of 3,051 male U.S. Air Force basic military trainees. Using a questionnaire, he obtained detailed information concerning subjects' ST use patterns before basic training. Clinical photos were taken of all leukoplakic lesions identified in ST users at the initial examination and again six weeks later. RESULTS: Of the 3,051 male trainees examined (mean age = 19.5 years), 9.9 percent (302/3,051) were identified as current ST users. Among current ST users, 39.4 percent (119/302) had leukoplakia vs. 1.5 percent (42/2,749) of nonusers of ST (odds ratio = 41.9, 95 percent confidence interval = 28.1-62.6). At the end of the involuntary cessation of tobacco use, 97.5 percent of these leukoplakic lesions had complete clinical resolution. The type of ST used (snuff vs. chewing tobacco), amount used (cans or pouches per day), length of use (months), number of days since last use and brand of snuff used were significantly associated with the risk of developing leukoplakic lesions among ST users. CONCLUSIONS: The important new finding from this investigation is that if a young, otherwise healthy man with leukoplakic lesions stops using tobacco for six weeks, most of his leukoplakic lesions will resolve clinically. Use of ST, specifically snuff, is strongly associated with development of oral leukoplakia in young adult men. CLINICAL IMPLICATIONS: The clinician can use these findings in deciding when to perform biopsies on leukoplakic lesions associated with ST use. This information also should be used to assist ST users in quitting this addictive behavior.

Adult↗
PubMed2005

Atypical protein kinase C is a novel mediator of dopamine-enhanced firing in nucleus accumbens neurons.

Current concepts suggest that nucleus accumbens (NAcb) dopamine mediates several motivated and addictive behaviors. Although the role of protein kinase A (PKA) and dopamine and cyclic adenosine 3',5' monophosphate-regulated phosphoprotein 32 kDa in NAcb dopamine receptor throughput has been studied extensively, the contribution of protein kinase C (PKC) to NAcb firing is poorly understood. Here we show that dopamine-mediated enhancement of spike firing in NAcb shell medium spiny neurons was prevented by the PKC inhibitor bisindolylmaleimide but not by the phospholipase C inhibitor 1-[6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione, suggesting a role for a diacylglycerol-independent atypical PKC (aPKC) isoform. In this regard, modulation of firing by dopamine was prevented by intracellular perfusion of a pseudosubstrate peptide inhibitor for aPKCs. We also provide evidence, using an in vitro kinase assay, that dopamine receptor activation increased aPKC activity in striatal membranes. Finally, direct activation of PKA with forskolin enhanced firing even during inhibition of aPKCs, suggesting that aPKCs acted upstream of PKA activation. Thus, aPKCs appear to mediate dopaminergic enhancement of spike firing in the NAcb shell, and may therefore play a critical role in NAcb- and dopamine-dependent goal-directed behaviors.

Action Potentials↗