Multiple interacting neural systems are involved in sustaining nicotine reinforcement. We and others have shown that dopamine D receptors and glutamate NMDA receptors both play important roles in nicotine reinforcement. Blockade of D receptors with the antagonist SCH-23390 (0.
View Article and Find Full Text PDFPharmacol Biochem Behav
April 2022
Nicotine and nicotinic compounds have been found to attenuate the attentional impairments caused by the glutamate NMDA antagonist dizocilpine (MK-801). The timing of the nicotine effect on attention in rodents has not yet been determined. In the current study, we tested the interaction of dizocilpine with nicotine.
View Article and Find Full Text PDFBackground: Nicotine has reinforcing effects, but there are thousands of other compounds in tobacco, some of which might interact with nicotine reinforcement.
Aims: This rat study was conducted to determine if nicotine self-administration is altered by co-administration of the complex mixture of compounds in tobacco smoke extract (TSE).
Methods: Female Sprague-Dawley rats were tested for self-administration of low doses of nicotine (3 or 10 µg/kg/infusion) at three different rates of reinforcement (FR1, FR3 and FR5) over three weeks either alone or together with the complex mixture of tobacco smoke extract (TSE).
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.
View Article and Find Full Text PDFOpioid use disorder (OUD) has a variety of adverse effects on both the users and their offspring. In the current study, a random group of Sprague-Dawley rats (25 females and 15 males) were tested for intravenous self-administration of the opioid agonist remifentanil to determine the range of acquisition for opioid. One-month after the end of self-administration of remifentanil, rats with the highest intake were mated together and rats with lowest intake were mated together.
View Article and Find Full Text PDFBackground: The Food and Drug Administration (FDA) is considering setting a nicotine standard for tobacco products to reduce their addictiveness. Such a standard should account for the apparent greater vulnerability to nicotine addiction in some subpopulations, such as adolescents with depression. The present study examined whether the reinforcement threshold and elasticity of demand (i.
View Article and Find Full Text PDFMaternal toxicant exposure during gestation can have deleterious effects on neurobehavioral development of the offspring. The potential risks engendered by paternal toxicant exposure prior to conception have been largely understudied. Recently, we found that chronic THC exposure prior to conception in male rats causes long-lasting behavioral impairment in their offspring.
View Article and Find Full Text PDFOpiate addiction has risen substantially during the past decade. New treatments to combat opiate addiction are sorely needed. The current study was conducted to determine the acute individual and interactive effects of bupropion and dextromethorphan in a rat model of opiate self-administration using the short-acting synthetic opioid remifentanil.
View Article and Find Full Text PDFRationale: A variety of neural systems are involved in drug addiction, and some of these systems are shared across different addictive drugs. We have found several different types of drug treatments that successfully reduce nicotine self-administration.
Objectives: The current set of studies is the first in a series to determine if drug treatments that have been found to significantly reduce nicotine self-administration would reduce opiate self-administration.
The potential health risks of cannabis are of growing concern, including effects on reproduction and development. Extensive research has investigated risks associated with maternal exposure to THC during gestation and its impacts on the development of offspring, but little research has been done regarding paternal THC exposure effects prior to conception. We have previously found that paternal THC exposure in rats causes changes in sperm methylation.
View Article and Find Full Text PDFA variety of neural systems are involved in the brain bases of tobacco addiction. Animal models of nicotine addiction have helped identify a variety of interacting neural systems involved in the pathophysiology of tobacco addiction. We and others have found that drug treatments affecting many of those neurotransmitter systems significantly decrease nicotine self-administration.
View Article and Find Full Text PDFNeurobehavioral bases of tobacco addiction and nicotine reinforcement are complex, involving more than only nicotinic cholinergic or dopaminergic systems. Memantine is an NMDA glutamate antagonist used to improve cognitive function in people with Alzheimer's disease. Glutamate may be an important component of the reinforcing effects of nicotine, so memantine was evaluated as a potential smoking cessation aid.
View Article and Find Full Text PDFIntroduction: Existing treatments can aid tobacco smoking cessation, but they have low efficacy. Because there is a network of neural systems involved in tobacco addiction, combination treatments may provide greater efficacy. Chronic nicotine and amitifadine have each been shown to significantly reduce nicotine self-administration in rats.
View Article and Find Full Text PDFStudies of intergenerational effects of parental chemical exposure have principally focused on maternal exposure, particularly for studies of adverse neurobehavioral consequences on the offspring. Maternal nicotine exposure has long been known to cause adverse neurobehavioral effects on the offspring. However, paternal toxicant exposure has also been found to cause neurobehavioral toxicity in their offspring.
View Article and Find Full Text PDFDevelopmental neurotoxicity of a wide variety of toxicants mediated via maternal exposure during gestation is very well established. In contrast, the impacts of paternal toxicant exposure on offspring neurobehavioral function are much less well studied. A vector for paternal toxicant exposure on development of his offspring has been identified.
View Article and Find Full Text PDFSazetidine-A selectively desensitizes α4β2 nicotinic receptors and also has partial agonist effects. We have shown that subcutaneous acute and repeated injections as well as chronic infusions of sazetidine-A significantly reduce intravenous (IV) nicotine self-administration in rats. To further investigate the promise of sazetidine-A as a smoking cessation aid, it is important to determine sazetidine-A effects with oral administration and the time-effect function for its action on nicotine self-administration.
View Article and Find Full Text PDFSazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a selective α4β2 nicotinic receptor desensitizing agent and partial agonist. Sazetidine-A has been shown in our previous studies to significantly reduce nicotine and alcohol self-administration in rats. The question arises whether sazetidine-A would reduce self-administration of other addictive drugs as well.
View Article and Find Full Text PDFTobacco addiction each year causes millions of deaths worldwide. Brain nicotinic acetylcholine receptors have been shown to be central to tobacco addiction. Nicotine replacement therapy aids tobacco cessation, but the success rate is still far too low.
View Article and Find Full Text PDFBackground: Although various pharmacological tools in combating addiction to alcohol are available, their efficacy is limited. Hence, there is a critical need for development of more effective medications. Recent advances in the field have identified the glutamatergic system as a potential novel target for intervention in addictive behaviors.
View Article and Find Full Text PDFA variety of nicotinic drug treatments have been found to decrease nicotine self-administration. However, interactions of drugs affecting different nicotinic receptor subtypes have not been much investigated. This study investigated the interactions between dextromethorphan, which blocks nicotinic α3β2 receptors as well as a variety of other receptors with sazetidine-A which is a potent and selective α4β2 nicotinic receptor partial agonist with desensitizing properties.
View Article and Find Full Text PDFSmoking cessation strategies are of prime medical importance. Despite availability of various pharmacological agents in combating addiction to nicotine, more effective medications are needed. Based on recent findings, the glutamatergic system in the brain may provide novel targets.
View Article and Find Full Text PDFRationale And Objectives: Desensitization of neuronal nicotinic acetylcholine receptors holds promise as an effective treatment of tobacco addiction. Previously, we found that sazetidine-A (Saz-A), which selectively desensitizes α4β2 nicotinic receptors, significantly decreased intravenous (IV) nicotine self-administration (SA) in rats with an effective dose of 3 mg/kg in acute and repeated injection studies. We also found that chronic infusions of Saz-A at doses of 2 and 6 mg/kg/day significantly reduced nicotine SA in rats.
View Article and Find Full Text PDFAm J Med Genet B Neuropsychiatr Genet
April 2017
Bipolar disorder (BD) is a common, recurring psychiatric illness with unknown pathogenesis. Recent studies suggest that microRNA (miRNA) levels in brains of BD patients are significantly altered, and these changes may offer insight into BD pathology or etiology. Previously, we observed significant alterations of miR-29c levels in extracellular vesicles (EVs) extracted from prefrontal cortex (Brodmann area 9, BA9) of BD patients.
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