Chronic infusions of mecamylamine into the medial habenula: Effects on nicotine self-administration in rats.
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2022-01
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Abstract
The habenula is an epithalamic structure through which descending connections go from the telencephalon to the brainstem, putting it in a key location to provide feedback control over the ascending projections from the brainstem to the telencephalon. The medial habenula has a high concentration of nicotinic receptors. We assessed the role of medial habenular nicotinic receptors for nicotine self-administration (SA) in female young adult Sprague-Dawley rats. The rats had bilateral chronic infusion cannulae placed into the medial habenula nucleus. Each cannula was connected to a slow delivery osmotic minipump to chronically infuse mecamylamine (100 µg/side/day) or vehicle for four consecutive weeks. The rats were tested for nicotine SA for the first two weeks of mecamylamine infusion. Then, they had one week of enforced abstinence, during which they had no access to the nicotine SA. Finally, they had one week of resumed nicotine SA access. There was a significantly differential mecamylamine effects in animals with lower and higher pretreatment baseline nicotine SA. Rats with lower baseline nicotine SA levels showed a nearly significant mecamylamine-induced reduction in SA while those with higher baseline levels of SA showed a significant mecamylamine-induced increase in nicotine SA. This study determined that medial habenular nicotinic receptors are important for nicotine reinforcement. Baseline level of performance makes a crucial difference for the involvement of habenular mechanisms in nicotine reinforcement with nicotinic activation being important for maintaining nicotine self-administration for those with lower levels of baseline self-administration and the opposite effect with subjects with higher levels of baseline self-administration.
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Levin, Edward D, Corinne Wells, Susan Slade, Joshua Johnson, Ann Petro, Amir H Rezvani and Jed E Rose (2022). Chronic infusions of mecamylamine into the medial habenula: Effects on nicotine self-administration in rats. Behavioural brain research, 416. p. 113574. 10.1016/j.bbr.2021.113574 Retrieved from https://hdl.handle.net/10161/29481.
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Edward Daniel Levin
Dr. Levin is Chief of the Neurobehavioral Research Lab in the Psychiatry Department of Duke University Medical Center. His primary academic appointment is as Professor in the Department of Psychiatry and Behavioral Sciences. He also has secondary appointments in the Department Pharmacology and Cancer Biology, the Department of Psychological and Brain Sciences and the Nicholas School of the Environment at Duke. His primary research effort is to understand basic neural interactions underlying cognitive function and addiction and to apply this knowledge to better understand cognitive dysfunction and addiction disorders and to develop novel therapeutic treatments.
The three main research components of his laboratory are focused on the themes of the basic neurobiology of cognition and addiction, neurobehavioral toxicology and the development of novel therapeutic treatments for cognitive dysfunction and substance abuse. Currently, our principal research focus concerns nicotine. We have documented the basic effects of nicotine on learning memory and attention as well as nicotine self-administration. We are continuing with more mechanistic studies in rat models using selective lesions, local infusions and neurotransmitter interaction studies. We have found that nicotine improves memory performance not only in normal rats, but also in rats with lesions of hippocampal and basal forebrain connections. We are concentrating on alpha7 and alpha4beta2 nicotinic receptor subtypes in the hippocampus, amygdala , thalamus and frontal cortex and how they interact with dopamine D1 and D2 and glutamate NMDA systems with regard to memory and addiction. I am also conducting studies on human cognitive behavior. We have current studies to assess nicotine effects on attention, memory and mental processing speed in schizophrenia, Alzheimer's Disease and Attention Deficit Hyperactivity Disorder. In the area of neurobehavioral toxicology, I have continuing projects to characterize the adverse effects of prenatal and adolescent nicotine exposure. Our primary project in neurobehavioral toxicology focuses on the cognitive deficits caused by the marine toxins. The basic and applied aims of our research complement each other nicely. The findings concerning neural mechanisms underlying cognitive function help direct the behavioral toxicology and therapeutic development studies, while the applied studies provide important functional information concerning the importance of the basic mechanisms under investigation.
Amir H. Rezvani
My research and teaching interests have been primarily focused on the following areas:
Alcoholism: I work with "alcoholic" rats with genetic predisposition!" We use selectively-bred alcohol preferring rats as an animal model of human alcoholism for developing better pharmacological treatments for alcoholism. Recently, we are working on several novel promising "anti-craving" compounds for the treatment of alcoholism. We are also studying the interaction between alcohol drinking and nicotine intake.
Nicotine Addiction: We have been studying age and sex differences in i.v. nicotine self-administration in rats. We have found that pattern of drug intake is both age- and sex-dependent. Our lab is also exploring different neuronal targets for developing better pharmacologic treatment for nicotine addiction.
Sustained Attention: Another aspect of our research is studying the role of the neuronal nicotinic and other neuronal systems in sustained attention using a rodent model. We have shown, nicotine (not smoking!) and nicotinic compounds improve attention in rats. A majority of people with schizophrenia smoke and they smoke heavily. Thus, it is important to understand the interaction of antipsychotic medications and nicotine in sustained attention. This has been another aspect of our research with interesting results. Presently, we are testing novel nicotinic compounds for improving pharmacologically-impaired sustained attention.
Teaching: I love to teach and interact with students. Since arriving at Duke in 1999, I have been team-teaching the popular alcohol course (Psych 206-01R; Alcohol: Brain, Society and Individual). I also enjoy mentoring undergrad students who are interested in science and enjoy working in the lab with cute little creatures!.
Community: I am a member of the Board of Directors of Triangle Residential Options for Substance Abusers (TROSA), a self-supported therapeutic community in Durham. I also give seminars and workshops on addiction around the country.
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