Evidence suggests a critical role for dopamine in the reinforcing effects of cocaine rats and primates. However, self-administration has been less often studied mouse species, and, to date, "knock-out" individual dopamine-related genes mice not reported reduce cocaine. We D1 receptor using combination gene-targeted mutation pharmacological tools. Two cohorts with varied breeding experimental histories were tested, both cohorts, there was significant decrease number knock-out that met...

Abstract Rationale Glucagon-like peptide-1 (GLP-1) receptor agonists reduce alcohol consumption in rodents and non-human primates. Semaglutide is a new long-acting GLP-1 agonist, widely used the clinic against type 2 diabetes obesity. It also reported to intake rodents. Objectives This study investigates possible inhibitory effect of semaglutide on alcohol-preferring African green monkeys. Methods We performed vehicle-controlled male monkeys that had demonstrated preference for alcohol. In...

The reinforcing effects of cocaine have been related to increased extracellular concentrations dopamine in the ventral striatum. Several studies suggest that M 5 muscarinic receptors facilitate striatal release. We tested hypothesis are decreased receptor-deficient mice using chronic intravenous self-administration extensively backcrossed mice. also assessed whether operant performance generally, rather than specifically, was altered mutant To this end, we evaluated both food-maintained...

There has been much interest in the relative importance of dopamine and serotonin transporters abuse-related-effects cocaine. We tested hypotheses that mice lacking transporter (DAT −/− ), (SERT or both SERT ) exhibit decreased reinforcing effects also assessed whether observed on self-administration are specific to cocaine if operant behavior maintained by food a direct agonist similarly affected. used broad range experimental conditions included acquisition without previous training,...

Abstract We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate procedure, we tested under variety environmental manipulations as well pharmacological pretreatments. Complete cocaine‐choice dose‐effect curves (0–1.0 mg/kg/infusion) were obtained for each condition concurrent fixed ratio schedules reinforcement. Percentage responding emitted on cocaine‐reinforced lever was not affected significantly by removal cocaine‐associated visual or...

Cocaine addiction is a worldwide public health problem for which there are no established treatments. The dopamine transporter (DAT) suspected as the primary target mediating cocaine9s abuse-related effects based on numerous pharmacological studies. However, in previous study, DAT knockout mice were reported to self-administer cocaine, generating much debate regarding importance of effects. Here, we show that expressing "knockin" cocaine-insensitive but functional did not cocaine...

Abstract Muscarinic cholinergic receptors of the M 5 subtype are expressed by dopamine‐containing neurons ventral tegmentum. These modulate activity midbrain dopaminergic neurons, which play an important role in mediating reinforcing properties abused psychostimulants like cocaine. The potential effects cocaine was investigated using receptor‐deficient mice a model acute self‐administration. ‐deficient self‐administered at significantly lower rate than wild‐type controls. In conditioned...

Chronic intravenous drug self-administration in rodents is a useful procedure for predicting the abuse liability of novel drugs humans, evaluating candidate treatments and dependence, studying biological basis addiction. This unit focuses on recent technical innovations conducting long-term studies i.v. behavior healthy, freely moving rats mice. Included are protocols construction, implantation, maintenance chronic indwelling jugular catheters, commentary critical parameters, troubleshooting...

Relative to intravenous drug self-administration, locomotor activity is easier measure with high throughput, particularly in mice. Therefore its potential predict differences self-administration between genotypes (e.g., targeted mutations, recombinant inbred strains) appealing, but such predictive value unverified. The main goal of this study was evaluate the utility assay for accurately predicting cocaine self-administration. A second any correlation a novel environment, and cocaine-induced...

Disturbances in central dopaminergic neurotransmission are believed to be centrally involved the pathogenesis of schizophrenia. Central and cholinergic systems interact muscarinic agonist xanomeline has shown antipsychotic effects clinical studies. Preclinical studies indicate that M 4 receptor subtype (mAChR) modulates activity system this specific mAChR is mediating antipsychotic-like xanomeline. A neuronal subpopulation expresses mAChRs together with D 1 dopamine receptors seems...

Tobacco use is associated with lethal diseases in an estimated 440,000 persons the United States each year (Centers for Disease Control and Prevention, 2005). Successful smoking quit-rates are at 5%-8%, even though a quarter of those attempts included smoking-cessation aids (Messer et al., 2008; Henningfield 2009). Current projections that 16% U.S. population-35 million people-will still smoke 2025, thus more effective urgently needed (Pollock The minor tobacco alkaloids may be promising...

Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to decrease ethanol (EtOH) drinking in rodent assays. The GLP-1 system also powerfully modulates food and fluid intake, gastrointestinal functions, metabolism. To begin understand the neurobiological mechanisms by which ligands may be able control EtOH it is important ascertain whether they can modulate direct reinforcing effects of EtOH, without confound on ingestive behaviors generally.

Abstract Dependence on opioids and the number of opioid overdose deaths are serious escalating public health problems, but medication-assisted treatments for addiction remain inadequate many patients. Glucagon-like pepide-1 (GLP-1) is a gut hormone neuropeptide with actions in peripheral tissues brain, including regulation blood glucose food intake. GLP-1 analogs, which approved diabetes medications, can reduce reinforcing rewarding effects alcohol, cocaine, amphetamine, nicotine rodents....

The neurotransmitter dopamine plays important roles in modulating cognitive, affective, and motor functions. Dysregulation of dopaminergic neurotransmission is thought to be involved the pathophysiology several psychiatric neurological disorders, including schizophrenia, Parkinson's disease drug abuse. Dopaminergic systems are regulated by cholinergic, especially muscarinic, input. Not surprisingly, increasing evidence implicates muscarinic acetylcholine receptor-mediated pathways as...

Alcohol use disorder remains a leading cause of preventable deaths, and current treatments have limited efficacy. Glucagon-like peptide 1 (GLP-1) receptor agonists can reduce alcohol drinking in preclinical studies, but mechanisms are still not fully understood, data female subjects scarce.