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PubMedDate not supplied

Sensitivity to the rewarding effects of food and exercise in the eating disorders.

The diminished capacity to experience pleasure or reward ("anhedonia") has its biological underpinnings in the mesolimbic dopamine system and is strongly implicated in risk for a variety of addictive behaviors. The present study tested the prediction that patients with anorexia nervosa (AN) would be more anhedonic than those with bulimia nervosa (BN)-a factor that could contribute to their respective avoidance and approach relationship to food. We also tested the idea that anhedonia would be correlated with high-level exercising from the viewpoint that the latter serves as a compensatory behavior for a blunted affect. AN patients of the restrictor subtype (n = 78) and BN patients with no history of AN (n = 76) were included in the regression analyses. Patients were also classified as excessive exercisers or moderate/nonexercisers according to information gathered during a structured clinical interview. Findings were largely supportive of our predictions. AN patients were highly anhedonic compared to BN patients, and excessive exercisers tended to be more anhedonic than those who did not exercise. We discuss the AN-BN differences in capacity for reward/pleasure in the context of the common psychobiological links between the eating disorders and drug and alcohol addiction, and speculate on how these differences might relate to the etiology and pathophysiology of both AN and BN.

Adult↗

PubMed1994

Reliability and validity of a brief patient-report instrument for psychiatric outcome evaluation.

OBJECTIVE: The authors describe the Behavior and Symptom Identification Scale (BASIS-32), a brief patient-report measure for psychiatric outcome assessment, and present the measure's factor structure and reliability and validity data. METHODS: Using the BASIS-32, interviews were conducted with a total of 387 patients shortly after their admission to the adult inpatient services of a private not-for-profit psychiatric hospital. Six months after admission, they received a follow-up questionnaire version of the instrument. RESULTS: Factor analysis of the instrument yielded five factors, on which subscales were based: relation to self and others, daily living and role functioning, depression and anxiety, impulsive and addictive behavior, and psychosis. Internal consistency of the subscales ranged from .63 to .80. Internal consistency of the full 32-item scale was .89. Test-retest reliability ranged from .65 to .81 for the five subscales. Concurrent and discriminant validity analyses indicated that the BASIS-32 ratings successfully discriminated patients hospitalized six months after admission from those living in the community, patients working at follow-up from those not working, and patients with particular diagnoses. Follow-up ratings indicated that the BASIS-32 is sensitive to changes in symptomatology and functioning. CONCLUSIONS: The BASIS-32 provides a brief, standardized assessment of symptoms and problems from the patient's perspective. The instrument can be used for outcome assessment with most psychiatric inpatients.

Activities of Daily Living↗

PubMed2003

Addicting drugs utilize a synergistic molecular mechanism in common requiring adenosine and Gi-beta gamma dimers.

The mesolimbic dopamine system and cAMP-dependent/protein kinase A (PKA) pathways are strongly implicated in addictive behaviors. Here we determine the role of dopamine D2 receptors (D2) in PKA signaling responses to delta-opioid (DOR) and cannabinoid (CB1) receptors. We find in NG108-15/D2 cells and in cultured primary neurons that a brief exposure to saturating concentrations of DOR and CB1 agonists increases cAMP, promotes PKA C alpha translocation and increases cAMP-dependent gene expression. Activation of PKA signaling is mediated by Gi-beta gamma dimers. Importantly, subthreshold concentrations of DOR or CB1 agonists with D2 agonists, which are without effect when added separately, together activate cAMP/PKA signaling synergistically. There is also synergy between DOR or CB1 with ethanol, another addicting agent. In all instances, synergy requires adenosine activation of adenosine A2 receptors and is mediated by beta gamma dimers. Synergy by this molecular mechanism appears to confer hypersensitivity to opioids and cannabinoids while simultaneously increasing the sensitivity of D2 signaling when receptors are expressed on the same cells. This mechanism may account, in part, for drug-induced activation of medium spiny neurons in the nucleus accumbens.

Adenosine↗

PubMed2005

A multicenter study of the revised Edmonton Staging System for classifying cancer pain in advanced cancer patients.

The comparative analysis of analgesic interventions for cancer pain is greatly compromised by the lack of well-validated and clinically acceptable tools, which allow a composite classification of pain and patient population characteristics. Although the Edmonton Staging System (ESS) for cancer pain was developed for this purpose, clinical and research utility has been limited due to problems associated with the assessment of some items, especially in relation to definitions and terminology. To overcome these limitations, we designed a revised ESS (rESS) and conducted a multicenter study to determine its inter-rater reliability and predictive value. In revising the rESS, we hypothesized that patients with less problematic pain features would require a shorter time to achieve stable pain control, require less complicated analgesic regimens, be more responsive to opioid therapy, and use lower opioid doses. The rESS items include mechanism of pain, presence or absence of incidental pain, presence or absence of psychological distress and addictive behavior, and level of cognitive function. Patients with cancer pain who were consecutively admitted to two different hospice centers, an acute care consultation service in a teaching hospital or a tertiary palliative care unit in a second teaching hospital were evaluated for study entry. Two independent palliative care specialists completed the rESS where possible within 24 hours of each other. Patients' pain ratings and opioid consumption were recorded daily until the study endpoint (i.e. achievement of stable pain control, discharge or death). Seven hundred and forty-six patients were eligible for study entry and of these, 619 (83%) had a pain syndrome. Inter-rater reliability estimates ranged from 0.67 (pain mechanism) to 0.95 (presence of addiction). In the univariate Cox regression analysis, younger patients (<60), as well as patients with neuropathic pain, incidental pain, psychological distress, or co-morbid psychological distress and addiction, required a significantly longer time to achieve stable pain control (P<0.05). In the multivariate Cox regression analysis, only age (<60), neuropathic pain and incidental pain were significantly associated with time to reach stable pain control (P<or=0.05). Patients with neuropathic or incidental pain used significantly more modalities to achieve stable pain control (P<0.01). Patients with neuropathic pain, incidental pain, as well as the presence of psychological distress or addiction, required a higher final mean morphine equivalent daily dose (MEDD) (P<0.001). A comparison of the rESS with the ESS demonstrated the ineffectiveness of the ESS prognostic staging system for predicting achievement of stable pain control. These findings confirm the study hypothesis, suggesting that the rESS appears to have good predictive value and a moderate to high inter-rater reliability. We suggest the rESS should prove to be a useful tool in clinical practice, and in the comparison of cancer pain populations in research studies.

Aged↗

PubMed2006

Characteristics of nosologically informative data sets that address key diagnostic issues facing the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) and International Classification of Diseases, eleventh edition (ICD-11) substance use disorders workgroups.

AIMS: Over the past two decades, many nosological issues have been addressed by the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD) substance use disorders workgroups. Even with those efforts, there are key issues that have not been resolved and must be revisited, or addressed de novo, by the workgroups. These lingering points are broad, due to the array of substances classified under the diagnostic umbrella of substance use disorders. They include substantive issues ranging from dimensional approaches, similar criteria for each substance, cut-points and thresholds, distinct abuse and dependence classifications, new criteria and drugs, to less substantive ones, such as the adjectives used to describe the severity of the behaviors. RESULTS: This paper describes the characteristics of the data sets that will be needed to resolve the key nosological issues. Ten points are described: (1) data must be true to nomenclature under study; (2) flexible regarding rearrangements of scoring algorithms; (3-4) able to assess substances individually and retain former versions of the criteria; (5) not rely on shortened versions; (6) utilize samples that are generalizable; (7) make diagnoses with transparent algorithms; (8) combine mixed methods for corroborating data; (9) utilize assessments that collect reliable and valid diagnoses and criteria; and (10) stretch the limits by allowing for new discoveries. CONCLUSIONS: This paper describes each of these and gives examples of the limitations and strengths of data for the purpose of defining a useful, unified concept of addictive behaviors.

Algorithms↗

PubMed1968

Behavioral engineering: the reduction of smoking behavior by a conditioning apparatus and procedure.

Recent findings from animal conditioning studies have revealed methods of reducing responses to a very low level with a minimum of aversive by-products. These findings were incorporated into the design of a cigarette case that automatically locked itself for a period of time after a cigarette was removed from it. The next cigarette could be taken at the end of the interval, which was signalled by distinctive stimuli. Five heavy smokers were allowed to become accustomed to using the case. Then, the duration for which the case was locked was gradually increased over a period of weeks to about 1 hr. Smoking gradually decreased to the target level of about one-half of a package of cigarettes per day. Control procedures showed that specific features of the apparatus were responsible for the reduction of smoking. The results indicated that this apparatus was sufficiently effective, convenient, and acceptable to smokers to constitute a practical procedure for reducing smoking to the level considered medically safe. The procedure may also have potential for reducing other habit-forming or addictive behaviors.

Journal Article↗

PubMed2002

Mutual mistrust in the medical care of drug users: the keys to the "narc" cabinet.

OBJECTIVE: Caring for patients who are active drug users is challenging. To better understand the often difficult relationships between illicit drug-using patients and their physicians, we sought to identify major issues that emerge during their interactions in a teaching hospital. DESIGN: Exploratory qualitative analysis of data from direct observation of patient care interactions and interviews with drug-using patients and their physicians. SETTING: The inpatient internal medicine service of an urban public teaching hospital. PARTICIPANTS: Nineteen patients with recent active drug use, primarily opiate use, and their 8 physician teams. RESULTS: Four major themes emerged. First, physicians feared being deceived by drug-using patients. In particular, they questioned whether patients' requests for opiates to treat pain or withdrawal might result from addictive behavior rather than from "medically indicated" need. Second, they lacked a standard approach to commonly encountered clinical issues, especially the assessment and treatment of pain and opiate withdrawal. Because patients' subjective report of symptoms is suspect, physicians struggled to find criteria for appropriate opiate prescription. Third, physicians avoided engaging patients regarding key complaints, and expressed discomfort and uncertainty in their approach to these patients. Fourth, drug-using patients were sensitive to the possibility of poor medical care, often interpreting physician inconsistency or hospital inefficiency as signs of intentional mistreatment. CONCLUSION: Physicians and drug-using patients in the teaching hospital setting display mutual mistrust, especially concerning opiate prescription. Physicians' fear of deception, inconsistency and avoidance interacts with patients' concern that they are mistreated and stigmatized. Medical education should focus greater attention on addiction medicine and pain management.

Adult↗

PubMedDate not supplied

Traumatic experiences and substance abuse: mapping the territory.

This article examines the relationships between various types of traumatic experiences and addictive behavior, with an eye to formulating effective treatment strategies. Interventions in the posttraumatic stress disorder (PTSD) and related fields are reviewed in an effort to understand how best to integrate them into substance abuse treatment. The recovery-oriented therapy model is used as a framework to define treatment tasks at each stage of the recovery process: how one addresses painful issues depends on the objective, given the recovery stage at hand. These tasks include making a commitment to abstinence, stopping alcohol and other drug use, consolidating abstinence and changing lifestyles, and addressing short- and long-term psychosocial issues. The article focuses on the clinical features of PTSD in an effort to enhance the practitioner's ability to address this disorder within the context of substance abuse treatment. Finally, recommendations are offered for training practitioners at varying skill levels in the addiction treatment field.

Adolescent↗

PubMed2004

Secrets of the opium poppy revealed.

Studies concerning drugs of abuse have made major contributions in defining the circuitry, as well as cellular and molecular substrates that underlie certain behaviors. Opiate drugs for example, have revealed important insights concerning pain perception and reward. Up to the late 1960s, opiate drugs were suspected to work by mysteriously perturbing lipid membrane structure. We now know the following: the sequence and neuroanatomy of the G-protein coupled receptors that mediate opiate effects; that many proteins interact with opioid receptors such as G-protein sub-unit combinations, G-protein receptor kinases, arrestins and calmodulin; that many signaling molecules are modulated by opioid receptors, including ion channels, kinase cascades and adenyl cyclase. More than 20 different peptides, excised from three precursor proteins by specific proteases, have been shown to be endogenous ligands for opioid receptors. Revealing the molecules of the endogenous opioid system has inspired efforts for developing new opioid analgesics with the hope of minimizing abuse potential. This article will detail the current rationale for searching for less-addictive opiate analgesics and speculate on the future of drug abuse research in furthering our understanding of neural plasticity and the underpinnings of addictive behavior.

Animals↗

PubMed1998

[Withdrawal therapy of patients with alcoholism and nicotine dependence with carcinomas in the area of the head and neck. Luxury or necessity?].

PURPOSE: Alcohol and nicotine abuse play a major role in the etiology of oral squamous cell carcinomas. In the present study, we investigated the number of patients with oral/oropharyngeal carcinomas who regularly consume alcohol and nicotine and what type of specific treatment should be prescribed for the addiction. PATIENTS AND METHOD: A total of 105 patients (90 men, 15 women) with oral/oropharyngeal squamous cell carcinomas were studied based on catamnestic data as well as a special questionnaire designed to assess drinking and smoking habits (40 g alcohol/day for men and 20 g alcohol/day for women was taken as the standard measure for those considered at risk for alcoholism). For smokers, the number of packs smoked per year was determined and compared to clinical data (i.e., tumor size, location) and laboratory data (gamma-GT). Particular attention was given to the addiction behavior before and after tumor therapy (recorded at least 1 year after successful tumor treatment). RESULTS: At the time of diagnosis, 83.1% regularly drank alcohol (71.9% reported drinking over 40 g/ 20 g of alcohol per day). Another 17.9% stopped drinking after therapy. Of the alcoholics 59.8% had been exposed to a daily consumption level above the threshold amount for more than 20 years. Some 70% of the patients reported that they exclusively drank beer. Tobacco consumption came from cigarette smoking 92.7% and 89.7% reported that they smoked before therapy--after therapy only 37.8% smoked. Carcinomas of the floor of the mouth indicated a prevalence toward alcohol and nicotine abuse. Of the patients with a T3 and T4 carcinoma 84% had daily alcohol consumption levels over the threshold value stated above. None of the 105 patients underwent specific alcohol treatment therapy. CONCLUSION: In light of the high prevalence of carcinomas of the oral cavity in patients with alcohol and nicotine addiction, mandatory withdrawal therapy should be offered in the form of postoperative treatment to prevent recurrence or the development of second primary tumors, as well as to improve the quality of life and encourage social rehabilitation. Before further treatment, for example, with retinoids, a successful withdrawal treatment should be completed.

Adult↗

PubMed2005

Alcohol consumption and the body's biological clock.

This review summarizes new findings on the bidirectional interactions between alcohol and the clock genes, underlying the generation of circadian rhythmicity. At the behavioral level, both adult and perinatal ethanol treatments after the free-running period and light response of the circadian clock in rodents; genetic ethanol preference in alcohol-preferring rat lines is also associated with alterations in circadian pacemaker function. At the neuronal level, it has been shown that ethanol consumption alters the circadian expression patterns of period (per) genes in various brain regions, including the suprachiasmatic nucleus. Notably, circadian functions of beta-endorphin-containing neurons that participate in the control of alcohol reinforcement become disturbed after chronic alcohol intake. In turn, per2 gene activity regulates alcohol intake through its effects on the glutamatergic system through glutamate reuptake mechanisms and thereby may affect a variety of physiological processes that are governed by our internal clock. In summary, a new pathologic chain has been identified that contributes to the negative health consequences of chronic alcohol intake. Thus, chronic alcohol intake alters the expression of per genes, and as a consequence, a variety of neurochemical and neuroendocrine functions become disturbed. Further steps in this pathologic chain are alterations in physiological and immune functions that are under circadian control, and, as a final consequence, addictive behavior might be triggered or sustained by this cascade.

Alcohol Drinking↗

PubMed1992

Episodic cluster headache. II: High tobacco and alcohol consumption in males.

Forty-nine out of 51 consecutive male patients with episodic cluster headache were studied with regard to their smoking and drinking habits in general and in relation to cluster headache periods. Questionnaires were constructed for data regarding tobacco intake. Situation-related smoking behavior was registered according to Frith (1971). Screening for alcohol over-consumption was made using the Malmö modification of the brief Michigan Alcoholism Screening Test (Mm-MAST). Eighty-three percent of the patients used tobacco on a regular basis at the time of the study, with an average consumption of 20 cigarettes per day. Only 3% had never used tobacco regularly. The smoking-related desire to smoke in different situations was consistent with what is found in a general population of smokers. Sixty-seven percent of the patients had scores on the Mm-MAST indicative of alcohol over-consumption (i.e. heavy social drinking or alcoholism). During active headache periods 79% decreased their alcohol intake, whereas no consistent change in tobacco consumption was reported for the group as a whole. These findings were further corroborated by the fact that alcohol, but not tobacco intake, was reported by the majority of patients to elicit headache attacks during periods. Thus, our study showed high alcohol and tobacco consumption to be prominent features in male patients with episodic cluster headache. Since neither alcohol nor tobacco appear to have properties of ameliorating headache periods or attacks, the addictive behavior in our patients more likely reflects certain personality characteristics.

Adolescent↗

PubMed2002

Ethanol stimulates cAMP-responsive element (CRE)-mediated transcription via CRE-binding protein and cAMP-dependent protein kinase.

Alcoholism is characterized by tolerance, dependence, and unrestrained craving for alcohol. Adaptive responses, including changes in gene expression in neurons, are thought to account for some of these complex behavioral abnormalities. We have shown in the NG108-15 neuroblastoma x glioma hybrid cell line that ethanol increases cellular cAMP levels via activation of adenosine A(2) receptors, leading to phosphorylation of the cAMP response element-binding protein (CREB). However, phosphorylation of CREB is not sufficient to activate cAMP response element (CRE)-mediated gene expression. Here we investigate whether ethanol increases CRE-mediated gene expression via endogenous CREB using a CRE-regulated luciferase reporter construct, transfected into NG108-15 cells. We find increased luciferase activity as a function of time of exposure to ethanol. Coexpression of a dominant-negative CREB construct blocked ethanol-stimulated CRE-luciferase expression, further suggesting that CREB is required for this response. We also determined whether ethanol-induced increases in gene expression are mediated by ethanol-induced increases in extracellular adenosine. We found that CRE-mediated gene expression induced by ethanol occurs in two phases: an early phase (4 h), in which adenosine receptor blockade prevents ethanol-induced gene expression, and a later phase (14 h), which is not blocked by an adenosine receptor antagonist. In both phases, inhibition of cAMP-dependent protein kinase A (PKA) activity prevented ethanol-induced CRE-mediated luciferase expression. Our data suggest that ethanol induces cAMP-dependent gene expression regulated by CREB and PKA and that this signaling pathway may mediate some of the addictive behaviors underlying alcoholism.

Animals↗

PubMed2000

Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors.

The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms. The net effect of neurotransmitter interaction at the mesolimbic brain region induces "reward" when dopamine (DA) is released from the neuron at the nucleus accumbens and interacts with a dopamine D2 receptor. "The reward cascade" involves the release of serotonin, which in turn at the hypothalmus stimulates enkephalin, which in turn inhibits GABA at the substania nigra, which in turn fine tunes the amount of DA released at the nucleus accumbens or "reward site." It is well known that under normal conditions in the reward site DA works to maintain our normal drives. In fact, DA has become to be known as the "pleasure molecule" and/or the "antistress molecule." When DA is released into the synapse, it stimulates a number a DA receptors (D1-D5) which results in increased feelings of well-being and stress reduction. A consensus of the literature suggests that when there is a dysfunction in the brain reward cascade, which could be caused by certain genetic variants (polygenic), especially in the DA system causing a hypodopaminergic trait, the brain of that person requires a DA fix to feel good. This trait leads to multiple drug-seeking behavior. This is so because alcohol, cocaine, heroin, marijuana, nicotine, and glucose all cause activation and neuronal release of brain DA, which could heal the abnormal cravings. Certainly after ten years of study we could say with confidence that carriers of the DAD2 receptor A1 allele have compromised D2 receptors. Therefore lack of D2 receptors causes individuals to have a high risk for multiple addictive, impulsive and compulsive behavioral propensities, such as severe alcoholism, cocaine, heroin, marijuana and nicotine use, glucose bingeing, pathological gambling, sex addiction, ADHD, Tourette's Syndrome, autism, chronic violence, posttraumatic stress disorder, schizoid/avoidant cluster, conduct disorder and antisocial behavior. In order to explain the breakdown of the reward cascade due to both multiple genes and environmental stimuli (pleiotropism) and resultant aberrant behaviors, Blum united this hypodopaminergic trait under the rubric of a reward deficiency syndrome.

Behavior, Addictive↗

PubMedDate not supplied

[Compliance in schizophrenia: predictive factors, therapeutical considerations and research implications].

Compliance has been defined as the extent to which a person's behavior coincides with the medical advice given. Medication compliance is one of the foremost problems affecting neuroleptic efficacy in psychiatric patients. Since chlorpromazine introduction in 1952, antipsychotics are the principal element of schizophrenia treatment. Actually progress links to the use of new antipsychotics are conditioned by quality of compliance. The problem of nonadherence to medication could concern 50% of prescription. The reported incidence of non-compliance with antipsychotic medication ranges from 11 to 80%. In a two thirds of case rehospitalization is the result of complete or partial noncompliance. After one year of first hospitalisation, 40% of relapse results from non adherence to medication. Medication adherence problems increase hospitalisation, morbidity and mortality. Social consequences, professional problems and family troubles linked to hospitalisations lead to low quality of life for patients and high cost for society. There are three main methods of measuring compliance. These include patient and clinical self-report, pill counts, and biological measures. Self-report methods are generally the most cost-effective and time-efficient way of obtaining an indication of compliance. In psychiatric research, the most commonly used self-report measure of compliance is the Drug Attitude Inventory (DAI) originally devised by Hogan et al. On the basis of criticism concerning DAI reliability, a new questionnaire of medication compliance was proposed: the Medication Adherence Rating scale (MARS). The main goal of compliance evaluation is to quantify this phenomenon with accuracy and to find predictive factors of medication nonadherence. Three types of factors influencing compliance are identified: factors due to medications, factors linked to patients and factors depending on the therapeutic relation with the clinician. Tolerance is considered as the principal reason explaining a bad compliance. Neurologic, endocrine and anticholinergic side-effects are the first fact of treatment stop. Medication prescription complexity is although important to take under consideration. Some psychotic's symptoms, comorbid addictive behavior, poor insight are mentioned in the case of noncompliance. Some effective actions to improve compliance are described. Information and communication with the patient, simplification of therapeutic plan, consultation planning and account of side effect are simple and effective actions. Social support is very important for improvement of compliance. The communication attitude of the clinician, therapeutic relation and prescription use are main points of compliance. Compared to a conventional care, psychoeducational programmes of compliance show their superiority. More research on compliance evaluation is needed. Information and tools must be proposed to practitioners.

Antipsychotic Agents↗

PubMed2005

A bio-behavioral model of addiction treatment: applying dual representation theory to craving management and relapse prevention.

A bio-behavioral approach to drug addiction treatment is outlined. The presented treatment model uses dual representation theory as a guiding framework for understanding the bio-behavioral processes activated during the application of expressive therapeutic methods. Specifically, the treatment model explains how visual processing techniques can supplement traditional relapse prevention therapy protocols, to help clients better manage cravings and control triggers in hard-to-treat populations such as chronic substance-dependent persons.

Art Therapy↗

PubMed1993

Suicide attempts in patients with panic disorder.

In a clinical sample of 100 outpatients with panic disorder, 42% had a history of suicide attempt. Female sex and being single, divorced, or widowed were associated with an increased risk of suicide attempt. Thirty-one (73.8%) of the suicide attempts occurred after the first panic attack and 27 (64.3%) after the onset of panic disorder. Eighty-eight of these patients met DSM-III-R criteria for at least one other diagnosis in addition to panic disorder. Moreover, 52% had a history of major depressive episode and 31% had a lifetime diagnosis of alcohol and/or other substance abuse. Compared with those who did not attempt suicide, those who attempted suicide were significantly more likely to have suffered from major depressive episode and alcohol or other substance abuse in their lifetime. Among the 35 patients with no comorbidity with either major depression or addictive behaviors, 17.1% had a history of suicide attempt. All had suffered from depressive symptoms and/or a personality disorder. The same association was found in four of 19 patients suffering from panic disorder only with or without agoraphobia.

Adult↗

PubMed1998

Inducibility of c-Fos protein in visuo-motor system and limbic structures after acute and repeated administration of nicotine in the rat.

To identify neuroanatomical substrates affected by nicotine, we have studied its effects after acute and repeated administration through the c-Fos protein inducibility in various brain structures. Ninety minutes after acute nicotine (0.35 mg/kg, s.c.) the number of c-Fos-like immunoreactive nuclei was consistently increased in visuo-motor structures such as the superior colliculus, the medial terminal nucleus of accessory optic tract, and the nucleus of the optic tract. The anteroventral and lateroposterior thalamic nuclei, connected with the retina and involved in limbic processing, showed a c-Fos induction. c-Fos was preferentially induced in terminal fields of neurons of the ventral tegmental area such as the nucleus accumbens, the central amygdala, the lateral habenula, the lateral septum, as well as the cingulate, medial prefrontal, orbital and piriform cortices. In chronically treated rats (0.35 mg/kg s.c., 3 x day for 14 days), the last nicotine injection given on the 15th day was still able to induce 90 minutes later c-Fos protein in visuo-motor, retino-limbic, subcortical, and cortical limbic structures. Moreover, this chronic treatment produced an additional recruitment of c-Fos-positive nuclei in the cingulate cortex, the core and the ventral shell of the nucleus accumbens. c-Fos induction after nicotine differs from that reported after other addictive drugs in terms of pattern and chronic inducibility, indicating that different mechanisms are involved for maintaining this transcription factor. In addition to a preferential sensitivity of mesolimbic dopaminergic neurons to nicotine, activation of visuo-limbic and limbic regions could be relevant for understanding some context-dependent and addictive behaviors produced by nicotine.

Aged↗