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PubMed1994

Group psychotherapy with spinal cord injured substance abusers.

Some studies have suggested that nondisabled people follow the dictates of a 'kindness norm' when reacting to those who are disabled. Spinal cord injured substance abusers have sometimes used the kindness of others to help maintain their addictive behavior. A special unit for such substance abusers in a Veterans Affairs hospital has used group psychotherapy as one of the principal methods for moving beyond the kindness norm and challenging its patients to struggle with their substance abuse. Therapists in this group have had to become aware of the special content of denial in this population, of the role of physical problems specific to spinal cord injury, and of the need to set aside clinical issues at times in order to make on the spot responses to practical problems associated with the injury.

Denial, Psychological↗

PubMed2004

Differential roles of 5-HT receptor subtypes in cue and cocaine reinstatement of cocaine-seeking behavior in rats.

The 5-HT indirect agonist, d-fenfluramine, attenuates cue reinstatement of extinguished cocaine-seeking behavior. To investigate the role of 5-HT receptor subtypes in this effect, we examined whether the attenuation is reversed by either a 5-HT(1A), 5-HT(2A/C), or 5-HT(2C) receptor antagonist. We also examined the effects of the antagonists alone on both cue and cocaine-primed reinstatement. Rats that had been trained to press a lever for cocaine (0.75 mg/kg/0.1 ml, i.v.) paired with light and tone cues underwent daily extinction sessions during which responding had no consequences. We then examined the effects of WAY 100635 (0-1.0 mg/kg, s.c.), ketanserin (0-10.0 mg/kg, i.p.), or SB 242,084 (0-1.0 mg/kg, i.p.) with and without d-fenfluramine (1.0 mg/kg, i.p.) pretreatment on cue reinstatement. Subsequently, we examined the effects of the antagonists on cocaine-primed (7.5 or 15.0 mg/kg, i.p.) reinstatement. The 5-HT(1A) antagonist, WAY 100635, failed to alter cue reinstatement, but attenuated cocaine reinstatement. Conversely, the 5-HT(2A/C) antagonist, ketanserin, attenuated cue reinstatement, but failed to alter cocaine reinstatement. The 5-HT(2C)-selective antagonist, SB 242,084, did not alter cue or cocaine reinstatement, but was the only drug that reversed the d-fenfluramine-induced attenuation of cue reinstatement. The findings suggest that stimulation of 5-HT(1A) receptors plays a critical role in cocaine-primed, but not cue, reinstatement. Furthermore, 5-HT(2A) and 5-HT(2C) receptors may play oppositional roles in cue reinstatement. The SB 242,084 reversal of the d-fenfluramine attenuation suggests that stimulation of 5-HT(2C) receptors inhibits cue reinstatement, whereas the ketanserin-induced attenuation of cue reinstatement suggests that decreased stimulation of 5-HT(2A) receptors inhibits this behavior.

Analysis of Variance↗

PubMed2004

Pharmacological blockade of alpha2-adrenoceptors induces reinstatement of cocaine-seeking behavior in squirrel monkeys.

Converging evidence suggests a role for noradrenergic mechanisms in stress-induced reinstatement of cocaine seeking in animals. Yohimbine, an alpha(2)-adrenoceptor antagonist, is known to be anxiogenic and induce stress-related responses in humans and animals. Here, we tested the ability of yohimbine to reinstate cocaine-seeking behavior and induce behavioral and physiological signs characteristic of stress in squirrel monkeys. Monkeys were trained to self-administer cocaine under a second-order schedule of i.v. drug injection. Drug seeking subsequently was extinguished by substituting saline for cocaine injections and omitting the cocaine-paired stimulus. The ability of yohimbine and the structurally distinct alpha(2)-adrenoceptor antagonist RS-79948 to reinstate cocaine-seeking behavior was assessed by administering priming injections immediately before test sessions in which the cocaine-paired stimulus was either present or absent. Priming injections of yohimbine (0.1-0.56 mg/kg, i.m.) or RS-79948 (0.01-0.1 mg/kg, i.m.) induced dose-related reinstatement of cocaine-seeking behavior. The magnitude of yohimbine-induced reinstatement was similar regardless of the presence or absence of the cocaine-paired stimulus. Yohimbine also significantly increased salivary cortisol levels, a physiological marker of stress, as well as scratching and self-grooming, behavioral markers of stress in nonhuman primates. In drug interaction experiments, pretreatment with the alpha(2)-adrenoceptor agonist clonidine (0.1-0.3 mg/kg, i.m.) dose-dependently inhibited yohimbine-induced reinstatement of cocaine seeking. In contrast, pretreatment with the dopamine receptor antagonist flupenthixol failed to inhibit yohimbine-induced reinstatement of cocaine seeking. The results show that pharmacological blockade of alpha(2)-adrenoceptors can induce reinstatement of cocaine-seeking behavior and characteristic stress responses in squirrel monkeys, providing a potentially useful model of stress-induced relapse to drug seeking.

Adrenergic alpha-Agonists↗

PubMed2004

Previous exposure to psychostimulants enhances the reinstatement of cocaine seeking by nucleus accumbens AMPA.

The effect of previous exposure to psychostimulants on the subsequent self-administration of cocaine as well as reinstatement of this behavior by priming infusions of AMPA into the nucleus accumbens (NAcc) was examined. Rats were exposed to five injections, one injection every third day, of either saline or amphetamine (AMPH: 1.5 mg/kg, i.p.). Starting 10 days later, they were trained to self-administer cocaine (0.3 mg/kg/infusion, i.v.) and subsequently tested under a progressive ratio (PR) schedule for 4 consecutive days. As expected, rats exposed to AMPH worked more and obtained more cocaine infusions than saline exposed controls on the PR test sessions. Following daily extinction sessions during which saline was substituted for cocaine, the effect of priming infusions of AMPA (0.0, 0.08, or 0.8 nmol/0.5 microl/side) into the NAcc was then examined on two tests: one conducted 4 days after the last cocaine PR test session (2-3 weeks after the last AMPH exposure injection) and the next 4 weeks later. Consistent with previous reports, NAcc AMPA dose-dependently reinstated cocaine seeking on both tests regardless of exposure condition. Importantly, this priming effect of NAcc AMPA was significantly enhanced in AMPH compared to saline exposed rats on the first test conducted 2-3 weeks after AMPH. On the second test, conducted 4 weeks after cocaine, reinstatement was similarly enhanced in both groups to levels observed on the first test in AMPH exposed rats. These results indicate that both noncontingent (AMPH) and contingent (cocaine) exposure to psychostimulants enhances the reinstatement of cocaine seeking by NAcc AMPA and appears to do so in a time-dependent manner.

Animals↗

PubMed2005

Administration of the D2 dopamine receptor antagonist sulpiride into the shell, but not the core, of the nucleus accumbens attenuates cocaine priming-induced reinstatement of drug seeking.

Enhanced dopamine transmission in the nucleus accumbens plays an important role in cocaine priming-induced reinstatement of drug-seeking behavior. However, the contribution of each dopamine receptor subtype to this behavior remains unclear. The present experiments were designed to assess the role of D2-like dopamine receptors in the nucleus accumbens core and shell subregions in cocaine priming-induced reinstatement of drug seeking. Rats were trained to lever press for cocaine using a fixed ratio (FR) 5 schedule of reinforcement. After approximately 18 days of cocaine self-administration, the animals underwent an extinction phase during which cocaine was replaced with saline. Daily extinction sessions were conducted until responding was less than 10% of the response rate maintained by cocaine self-administration. Following the extinction phase, priming-induced reinstatement of cocaine-seeking behavior was assessed. A range of doses of antagonists selective for D2- (sulpiride, 0.2 or 2.0 microg), D3- (U99194A, 3.9 or 7.8 microg), or D4- (L-750,667, 5.5 or 11 microg) dopamine receptors were microinjected into either the nucleus accumbens core, shell or lateral septum prior to a priming injection of cocaine (10 mg/kg, i.p.). Following administration into the shell, but not core or lateral septum, sulpiride dose-dependently attenuated reinstatement induced by a cocaine priming injection. In contrast, U99194A and L-750,667 failed to influence cocaine seeking at any of the doses tested in either accumbal subregion. Collectively, these findings indicate that activation of D2 dopamine receptors mediates cocaine priming-induced reinstatement of cocaine seeking in a region-specific manner within the nucleus accumbens.

Analysis of Variance↗

PubMed2006

DHEA, a neurosteroid, decreases cocaine self-administration and reinstatement of cocaine-seeking behavior in rats.

Dehydroepiandrosterone (DHEA), which can act as a potential antidepressant in both animals and humans, appears to lower distress involved with cocaine withdrawal. In fact, a role for neurosteroids in modulation of substance-seeking behavior is becoming increasingly clear. Therefore, we tested the effects of DHEA on the self-administration of cocaine (1 mg/kg/infusion) by rats. At maintenance, a relatively low dose of exogenous DHEA (2 mg/kg; i.p.) attenuated cocaine self-administration after several days of chronic treatment. More than 2 weeks (19 days) of daily DHEA injections were required to decrease the cocaine-seeking behavior of rats to less than 20% of their maintenance levels. DHEA does not seem to decrease cocaine self-administration by increasing the reinforcing properties of the drug, as indicated by a cocaine dose-response determination. After being subjected to extinction conditions in the presence of DHEA, rats demonstrated a minimal response to acute exposure to cocaine (10 mg/kg), which indicated a protective effect of DHEA on relapse to cocaine usage. Our results suggest a potential role for the neurosteroid DHEA in controlling cocaine-seeking behavior, by reducing both the desire for cocaine usage and the incidence of relapse.

Adjuvants, Immunologic↗

PubMed2006

Heroin-induced reinstatement is specific to compulsive heroin use and dissociable from heroin reward and sensitization.

Increased drug availability can precipitate a rapid transition to compulsive drug use in both vulnerable humans and laboratory animals. Recent studies have shown that despite equivalent levels of psychomotor sensitization, only rats with prolonged, but not limited, access to cocaine self-administration respond to the priming effects of cocaine on drug seeking, as measured in a within-session reinstatement model of drug craving. In this model, drug seeking is first extinguished and then reinstated by non-contingent presentations of the drug alone in the absence of response-contingent stimuli. Here, we assessed the generality of this observation in rats with daily short (1 h, ShA) vs long access (6 h, LgA) to i.v. heroin self-administration. As expected, heroin intake by LgA rats (n=24) increased over time to become excessive compared to heroin intake by ShA rats (n=24). After escalation, LgA rats tended to be less sensitive to heroin-induced locomotion (7.5-30 microg, i.v.) than ShA rats. In contrast, only LgA rats, not ShA rats, responded to the priming effects of heroin, as measured by the ability of heroin alone (7.5-30 microg, i.v.) to reinstate extinguished drug-seeking behavior. Finally, during the course of heroin intake escalation, a large proportion of LgA rats developed self-injury (mostly targeting the nails and digit tips of the forepaws), a negative consequence not seen in ShA rats. This study reproduces and extends previous research on compulsive cocaine use by showing that heroin-induced reinstatement is also specific to compulsive drug use and dissociable from heroin-induced reward and psychomotor sensitization.

Animals↗

PubMed2005

Dopamine receptor DRD2 genotype and smoking cessation outcome following treatment with bupropion SR.

The A1 allele of the dopamine D2 receptor gene (DRD2) is associated with a reduced number of dopamine binding sites in the brain and with the increased likelihood of substance abuse and addictive behavior. In a study of smokers enrolled in an open-label, randomized effectiveness trial, we investigated whether variants in the DRD2 receptor gene are associated with smoking cessation outcomes following treatment with a combination of bupropion SR and behavioral counseling. Adherence to treatment and point-prevalent smoking status were assessed at 3 and 12 months, respectively, following a target quit date. Compared to women who carry both A2 alleles, women with at least one A1 allele were more likely to report having stopped taking bupropion due to medication side effects (odds ratio (OR)=1.91, 95% confidence interval (CI)=1.01-3.60; P<0.04) and at 12 months were somewhat more likely to report smoking (OR=0.76, 95% CI=0.56-1.03; P<0.076). Significant associations or trends were not observed in men. In women, individual variability in responsiveness to bupropion-based treatment may be partially due to differences in genetic variants influencing dopamine receptor function.

Adult↗

PubMed2002

Fermenting fruit and the historical ecology of ethanol ingestion: is alcoholism in modern humans an evolutionary hangover?

In the field of addiction research, the possibility of ancestral exposure to psychoactive compounds has generally been excluded. A paleobiological approach to the human diet, however, illustrates the potential utility of historical data in interpreting modern-day addictive behaviors. Low-level dietary exposure to ethanol via ingestion of fermenting fruit has probably characterized the predominantly frugivorous anthropoid lineage for about 40 million years. Potentially adaptive primate behaviors associated with the natural occurrence of ethanol include the olfactory use of ethanol plumes to localize fruit crops, the use of ethanol as an appetitive stimulant to facilitate rapid consumption of transient nutritional resources, and the physiological exploitation of the caloric benefits of ethanol. Such behavioral and energetic advantages probably pertain to all animal taxa that consume fermenting fruit, and may have been retained in modern humans in spite of considerable dietary diversification over the last several million years. In contemporary human environments, excessive consumption of ethanol would then represent maladaptive cooption of ancestrally advantageous behaviors given essentially ad libitum access to a compound otherwise found only within scarce nutritional substrates. Epidemiologically demonstrated health benefits of low-level alcohol consumption are consistent with an ancient and potentially adaptive exposure of primate frugivores to this most common of the psychoactive substances.

Alcoholism↗

PubMed2000

Opioid receptors: from genes to mice.

Opiates produce their strong analgesic and addictive actions by activating mu-, delta-, and kappa-opioid receptors, which otherwise interact with endogenous opioid peptides to regulate nociception, mood, and responses to stress. The recent cloning of an opioid receptor gene family has allowed the production of null-mutant mice for each mu-, delta-, and kappa-receptor gene. Initial observation of receptor-deficient mice shows no obvious developmental abnormality, and reveals subtle modifications of pain perception in adult mice. Pharmacologic responses to standard opiates have been evaluated carefully, and results suggest that morphine produces its main biologic actions by acting specifically at mu-receptors, whereas delta-agonists seem weakly delta-selective under in vivo experimental conditions. Future studies of single- and combinatorial-opioid receptor-deficient mice will clarify the specific role of each receptor in chronic pain, motivation, and addictive behaviors. These mice also represent useful tools in the development of novel opioid compounds of therapeutic interest.

Journal Article↗

PubMedDate not supplied

Opioid receptor genes inactivated in mice: the highlights.

The opioid system controls nociception, stress responses, and addictive behaviors. Exogenous alkaloid opiates and endogenous opioid peptides stimulate mu-, delta- and kappa-opioid receptors, whose activities have long been analyzed by pharmacological tools. Mice lacking opioid receptor and opioid peptide precursor genes have now been produced by gene targeting. Behavioral analysis of mutant animals in the absence of drug has highlighted a distinct role of opioid receptors or peptides in nociception and revealed an important role for delta receptors in emotional behaviors. The examination of responses to drugs has clarified involvement of each receptor as molecular targets for exogenous opiates in vivo. Those data have also demonstrated the critical role of mu-receptor in cannabinoid and alcohol reinforcement and confirmed the involvement of kappa receptor in several dysphoric responses. Ongoing studies therefore help in understanding the molecular basis of opioid-controlled behaviors and will contribute to the development of novel therapeutics for pain, anxiety, and drug abuse.

Affect↗

PubMed2006

Cocaine-induced dendritic spine formation in D1 and D2 dopamine receptor-containing medium spiny neurons in nucleus accumbens.

Psychostimulant-induced alteration of dendritic spines on dopaminoceptive neurons in nucleus accumbens (NAcc) has been hypothesized as an adaptive neuronal response that is linked to long-lasting addictive behaviors. NAcc is largely composed of two distinct subpopulations of medium-sized spiny neurons expressing high levels of either dopamine D1 or D2 receptors. In the present study, we analyzed dendritic spine density after chronic cocaine treatment in distinct D1 or D2 receptor-containing medium-sized spiny neurons in NAcc. These studies made use of transgenic mice that expressed EGFP under the control of either the D1 or D2 receptor promoter (Drd1-EGFP or Drd2-EGFP). After 28 days of cocaine treatment and 2 days of withdrawal, spine density increased in both Drd1-EGFP- and Drd2-EGFP-positive neurons. However, the increase in spine density was maintained only in Drd1-EGFP-positive neurons 30 days after drug withdrawal. Notably, increased DeltaFosB expression also was observed in Drd1-EGFP- and Drd2-EGFP-positive neurons after 2 days of drug withdrawal but only in Drd1-EGFP-positive neurons after 30 days of drug withdrawal. These results suggest that the increased spine density observed after chronic cocaine treatment is stable only in D1-receptor-containing neurons and that DeltaFosB expression is associated with the formation and/or the maintenance of dendritic spines in D1 as well as D2 receptor-containing neurons in NAcc.

Animals↗

PubMed1990

Learned resourcefulness, drinking, and smoking in young adults.

The purpose of this study was to examine the relationship between learned resourcefulness and two common addictive behaviors, namely, drinking and smoking. Male and female college students (N = 175) completed the Self-Control Schedule (SCS), the Quantity-Frequency-Variability questionnaire, and a smoking history form. Learned resourcefulness was related to self-reported patterns of alcohol consumption; specifically, heavy drinking subjects were lower in learned resourcefulness than were light and moderate drinkers who, in turn, were lower in learned resourcefulness than were infrequent drinkers and abstainers. Learned resourcefulness was only modestly related to smoking, with students who had never smoked evidencing somewhat higher learned resourcefulness than ex-smokers and current smokers. Overall, these data provide correlational support for the notion that learned resourcefulness may protect young adults against substance abuse.

Adult↗

PubMed1983

Conceptual factors in the treatment of paraphilias: a preliminary report.

The purpose of this paper is to discuss conceptual components of treating paraphilia. Detailed description of the treatment interventions will be published subsequently. The format of the psychotherapy has components similar to the programs for sexual dysfunction and homosexual dissatisfaction therapy. Intensive short-term directive conjoint therapy remains essential. The therapeutic model focuses on the paraphilia as an interpersonal relationship disorder which is manifested as an unproductive and sometimes addictive means of coping with stress, particularly engendered by discomfort with intimacy in adult erotic relationships. The basic model of psychotherapy includes specific intervention directed at potential social skill deficits, changing erotic imagery, attitude and cognitive restructuring, self-esteem difficulties, dating anxiety, sexual dysfunction, intimacy issues and addictive behavior, all of which encourage mastery, self-assertion, self-responsibility and communication skills within the context of a relationship.

Arousal↗

PubMedDate not supplied

Drug treatment effectiveness: African-American culture in recovery.

African-Americans are overrepresented among drug abusers in the United States when compared to European-Americans, and have lower rates of recovery from drug addiction after treatment. There has been no comprehensive research to date to specifically explain either this overrepresentation or lower rates of recovery among African-Americans. In this article, it is suggested that one reason for this lack of attention is due to the failure of drug abuse treatment providers and researchers to see race as a cultural rather than physical phenomenon. The point is made that cultural factors are intrinsic to successful efforts to address drug abuse among African-Americans. Several historic African-American coping strategies are outlined and shown to be powerful factors in client addictive behavior and barriers to recovery. Through case studies of clients who were successful in their effort to recover, the necessity to address cultural as well as personal issues is shown to be vital to successful recovery among African-Americans.

Adult↗

PubMedDate not supplied

Treatment of dually diagnosed clients.

Up to 80% of people with mental and emotional disorders have abused or will abuse street drugs or alcohol at some point in their lives. Similarly, over half of people with substance use disorders are also diagnosed with a mental disorder at some point. In clinical populations and institutional settings, the numbers are far higher. The term dual diagnosis (coexisting mental and substance use disorders) refers to a large and complex group of people. This article addresses general issues regarding the complexities of dual diagnosis--differential diagnosis, the difficulty of achieving abstinence for people who perceive significant benefits from drug use, and the problems due to the historical split between the mental health and substance abuse treatment systems. Harm reduction, an approach to treating drug-using clients that focuses on the damage done by drugs and alcohol without insisting on abstinence from all psychoactive substances, can offer a useful way of conceptualizing treatment of dual diagnosis. A treatment group specifically designed for dually diagnosed clients is described. This group, inspired by the idea that changes in addictive behavior occur in a series of stages and that motivation can be influenced by the quality of the relationship with the treatment provider, uses a drop-in structure to provide low-threshold access to supportive treatment, to meet clients "where they are."

Diagnosis, Dual (Psychiatry)↗

PubMed2000

Dietary change through African American churches: baseline results and program description of the eat for life trial.

BACKGROUND: Eat for Life, a multicomponent intervention to increase fruit and vegetable (F & V) consumption among African Americans, is delivered through African American churches. METHODS: Fourteen churches were randomly assigned to one of three treatment conditions: 1) comparison; 2) culturally-sensitive multicomponent intervention with one phone call; and 3) culturally-sensitive multicomponent intervention with four phone calls. The intervention included an 18-minute video, a project cookbook, printed health education materials, and several "cues" imprinted with the project logo and a 5 A Day message. A key element of the telephone intervention was the use of motivational interviewing, a counseling technique originally developed for addictive behaviors. Major outcomes for the trial included total F & V intake, assessed by food-frequency questionnaires (FFQs) and 24-hour recalls, and serum carotenoids. Psychosocial variables assessed included outcome expectations, barriers to F & V intake, preference for meat meals, neophobia, social support to eat more F & V, self-efficacy to eat more F & V, and nutrition knowledge. RESULTS: Baseline mean F & V intakes across the three FFQs ranged from 3.45 to 4.28 servings per day. Intake based on a single 24-hour recall was 3.0 servings. Variables positively correlated with F & V intake included self-efficacy, outcome expectations, and a belief that F & V contain vitamins. Factors negatively correlated with intake include perceived barriers, meat preference, neophobia, and high-fat cooking practices. The completion rate for the first telephone counseling call was 90%. Completion rates for the remaining three calls ranged from 79% to 86%. CONCLUSION: The recruitment and intervention methods of the Eat for Life study appear promising. The telephone intervention based on motivational interviewing is potentially useful for delivering dietary counseling.

Adult↗

PubMed2000

Innovative Clinical Addiction Research Training Track in Preventive Medicine.

Medical education related to identification, diagnosis and management of alcohol and other drug problems receives inadequate attention in the undergraduate curriculum and during residency training. This article describes the design, implementation, and evaluation of a new track in Clinical Addiction Research Training (CART) in a General Preventive Medicine (GPM) residency program. CART is comprised of a new course in Addiction Medicine, new practicum sites in addiction medicine research and treatment, and a CART-designated resident. An Advisory Group of educators, researchers, scholars, and administrators in addiction medicine, has provided guidance and support for this new track. Evaluation of the CART track suggested improvements in residents' knowledge and attitudes. Residents engaged in high caliber clinical addiction research projects. The development of the CART track within the GPM residency is an approach that can be integrated into other specialties, such as internal medicine, family practice, and adolescent medicine, to develop residents' interest and expertise in the addictive behaviors.

Journal Article↗