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L D Karan

Publications and source records attributed to L D Karan.

10 recordsLinked to original sources

Discriminative stimulus (DS) properties of nicotine in the C57BL/6 mouse.

Previous research conducted in this and other laboratories has examined the role of genetic factors in determining sensitivity to (-)-nicotine in a variety of behavioral and physiological measures in the rat. More recent research further indicates that genetic factors can also influence the level of sensitivity to (-)-nicotine when serving as a discriminative stimulus (DS) in different rat strains. However, there has been little work examining the influence of genotype on the discriminative stimulus (DS) properties of (-)-nicotine in mice, a species that has played a major role in understanding the relationship between genetics and (-)-nicotine pharmacological effects. To further our understanding of the role of genetics and the ability of (-)-nicotine to exert DS control of behavior in the mouse, a group of C57BL/6 mice was trained to discriminate 0.4 mg/kg (-)-nicotine from saline using a two-lever operant procedure. (-)-Nicotine's discriminative stimulus in C57BL/6 mice appears to be similar to that generated in the rat. Results from behavioral tests with other drugs indicated that d-amphetamine exhibited a partial generalization, while (+)-nicotine fully generalized with nicotine. Tests of antagonism with mecamylamine and scopolamine further showed the cholinergic specificity of the (-)-nicotine DS in the mouse; mecamylamine but not scopolamine completely antagonized the (-)-nicotine DS. This work lays the groundwork for future comparisons of different mouse strain's sensitivities to (-)-nicotine's discriminative stimulus as well as using this behavioral model to search for new nicotinic receptor agonists and antagonists.

Analysis of Variance↗

Nicotine-induced acute tolerance: studies involving schedule-controlled behavior.

The major goal of the present study was to examine acute tolerance to nicotine-induced disruption of operant behavior following a single, noncontingent injection. Rats were trained to lever press for food reinforcement under a fixed ratio-30 schedule. Once trained, rats were injected with either saline or nicotine (0.8 mg/kg) in their home cages. After either a 90- or 180-min delay, each rat was injected with nicotine (0.4 mg/kg) and placed in the operant chamber for a 30-min behavioral evaluation session. This experiment was replicated with slight modifications 1 week later. The results of the present study suggest that 0.8 mg/kg of nicotine produces acute tolerance to the response rate decreasing effects of 0.4 mg/kg of nicotine. Because the tolerance-producing dose of nicotine was injected while rats were not in the test environment, they did not have an opportunity to practice the target behavior while under the influence of the drug. Hence, the acute tolerance observed in this study appears to be, at least partly, pharmacological (vs. behavioral) in nature, and may be related to a desensitization of central nicotinic acetylcholinergic receptors (nAChRs).

Animals↗

Substance abuse.

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Humans↗

Primary care for AIDS and chemical dependence.

Primary care clinicians are acquiring an increasingly important role in preventing, diagnosing, and treating both chemical dependence and human immunodeficiency virus (HIV) illness. Towards this end they need to know the epidemiology of HIV infection in chemically dependent persons and methods of educating persons at high risk for these problems. It is critical that physicians screen for alcohol and drug addiction. Health care providers should understand the risks and benefits of HIV antibody testing and include in their practices the basic components of counseling before and after testing and informed consent. Both HIV illness and addiction are chronic diseases with long-term health implications. A knowledge of patient characteristics, intensity of treatments, and treatment modalities is important in making recommendations for individualized therapy. Combining service delivery is a future challenge necessitated by today's joint epidemics of the acquired immunodeficiency syndrome and chemical dependence.

Acquired Immunodeficiency Syndrome↗

Substance abuse.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Initial encounters with tobacco cessation on the Inpatient Substance Abuse Unit of the Medical College of Virginia.

When the Medical College of Virginia became a smoke-free facility on May 1, 1990, the inpatient unit of the Division of Substance Abuse Medicine decided that it would require tobacco abstinence of its patients, and that it would treat nicotine addiction in a similar fashion as other chemical dependencies. Surreptitious alcohol and drug use on the unit was minimal, but clandestine cigarette smoking prevailed. The succeeding restrictive environment and enforcement efforts became counterproductive. Beginning December 23, 1990, the inpatient unit decided to re-allow smoking. A motivational curriculum for all patients and an optional cessation program for those patients who wish to quit smoking during their inpatient stay is planned. Methods to effectively address nicotine addiction during chemical dependency treatment need to continually be refined and explored.

Adult↗

Neurobehavioral mechanisms of nicotine action: role in the initiation and maintenance of tobacco dependence.

Basic neuroscience research conducted over the last quarter century has provided us with much information concerning potential biobehavioral and neuromolecular mechanisms involved in the initiation and maintenance of tobacco dependence. Nicotinic-acetylcholinergic receptors (AChRs), in addition to having a primary locus on cholinergic neurons, appear to be also located on a variety of noncholinergic neurons (presynaptic and/or postsynaptic sites). Nicotine therefore appears to be able to affect a variety of neuronal pathways involved in behavioral reward and arousal processes, which appear paramount to tobacco dependence. Nicotine appears to have several unique properties at the cellular level that allow it to act both as an agonist and as a potential antagonist at select AChRs. Nicotine's ability to act as an agonist appears to be contingent on an action at nAChRs, which initially open a receptor-linked cation channel, eliciting the entrance of CA++ (or other cations) into the cell. Cation entrance into the cell, therefore, may be the cellular transducer of nicotine's behavioral and dependence-producing effects. Subsequent to this initial agonist effect, the nicotinic receptor is believed to undergo a refractory period, via a desensitization process, during which Ca++ is prevented from further entrance into the cell. It is this ability to induce receptor desensitization which seems central to nicotine's ability to act as an antagonist. The duration of nAChR desensitization may also be useful in explaining individual variability to nicotine's behavioral effects and may be related to the induction of acute and/or chronic tolerance in both animals and man. Nicotine-induced desensitization may also be important to relapse in the smoker if conditioned stimuli are able to provoke such mechanisms, which could lead to the need to smoke. Finally, a model is presented to account for individual smoking patterns and level of tobacco dependence which is partially based on the proposed cellular mechanisms of nicotine action and desensitization at the nAChR.

Animals↗

AIDS prevention and chemical dependence treatment needs of women and their children.

Female partners of male drug users may not recognize that they are endangered by sexual transmission of human immunodeficiency virus (HIV). However, even when women acknowledge this problem, there are multiple subsequent impediments to behavior change. Chemically dependent women also have specific additional needs. Most chemical dependence outreach and treatment programs are not yet designed to address the issues of contraception, pregnancy, motherhood, child rearing, and prevention of sexually transmitted diseases. Chemically dependent women may not only give birth to drug-affected infants but they may also perpetuate an intergenerational cycle of inadequate parenting. Most women at risk for HIV infection are in their childbearing years. Infection of either or both mother and infant further complicates an already complex problem. Multiple interdisciplinary resources are needed to integrate AIDS prevention and treatment with chemical dependence treatment for women and their children.

Acquired Immunodeficiency Syndrome↗

Substance abuse treatment modalities in the age of HIV spectrum disease.

AMSAODD's Third National Forum on AIDS and Chemical Dependency presented a session about the theory and practicality of combining pharmacologic and nonpharmacologic treatment modalities to maximize the social, psychological, and physical health of patients. Synthesizing methadone maintenance for opioid dependence with abstinence modalities for cocaine dependence and alcoholism was discussed. Chronic adequate methadone treatment allows normalization of neuroendocrine function, is associated with normal natural killer-cell activity, and has proven efficacious in retaining patients in chemical dependence treatment, and thus decreasing the risk for transmission of HIV infection. Individualization of treatment is then exemplified by four clinical vignettes that were discussed by a panel of experts.

Adult↗