Dataset Information

Cannabinoid receptor blockade reduces the opportunity cost at which rats maintain operant performance for rewarding brain stimulation.

ABSTRACT: There is ample evidence that blockade of CB(1) receptors reduces reward seeking. However, the reported effects of CB(1) blockade on performance for rewarding electrical brain stimulation stand out as an exception. By applying a novel method for conceptualizing and measuring reward seeking, we show that AM-251, a CB(1) receptor antagonist, does indeed decrease performance for rewarding electrical stimulation of the medial forebrain bundle in rats. Reward seeking depends on multiple sets of variables, including the intensity of the reward, its cost, and the value of competing rewards. In turn, reward intensity depends both on the sensitivity and gain of brain reward circuitry. We show that drug-induced changes in sensitivity cannot account for the suppressive effect of AM-251 on reward seeking. Therefore, the role of CB(1) receptors must be sought among the remaining determinants of performance. Our analysis provides an explanation of the inconsistencies between prior reports, which likely arose from the following: (1) the averaging of data across subjects showing heterogeneous effects and (2) the use of methods that cannot distinguish between the different determinants of reward pursuit. By means of microdialysis, we demonstrate that blockade of CB(1) receptors attenuates nucleus accumbens dopamine release in response to rewarding medial forebrain bundle stimulation, and we propose that this action is responsible for the ability of the drug to decrease performance for the electrical reward.

SUBMITTER: Trujillo-Pisanty I

PROVIDER: S-EPMC5824329 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cannabinoid receptor blockade reduces the opportunity cost at which rats maintain operant performance for rewarding brain stimulation.

Trujillo-Pisanty Ivan I Hernandez Giovanni G Moreau-Debord Ian I Cossette Marie-Pierre MP Conover Kent K Cheer Joseph F JF Shizgal Peter P

The Journal of neuroscience : the official journal of the Society for Neuroscience 20110401 14

There is ample evidence that blockade of CB(1) receptors reduces reward seeking. However, the reported effects of CB(1) blockade on performance for rewarding electrical brain stimulation stand out as an exception. By applying a novel method for conceptualizing and measuring reward seeking, we show that AM-251, a CB(1) receptor antagonist, does indeed decrease performance for rewarding electrical stimulation of the medial forebrain bundle in rats. Reward seeking depends on multiple sets of variab ...[more]

PMID: 21471378

Similar Datasets

Project description:Pursuit of one goal typically precludes simultaneous pursuit of another. Thus, each exclusive activity entails an "opportunity cost:" the forgone benefits from the next-best activity eschewed. The present experiment estimates, in laboratory rats, the function that maps objective opportunity costs into subjective ones. In an operant chamber, rewarding electrical brain stimulation was delivered when the cumulative time a lever had been depressed reached a criterion duration. The value of the activities forgone during this duration is the opportunity cost of the electrical reward. We determined which of four functions best describes how objective opportunity costs, expressed as the required duration of lever depression, are translated into their subjective equivalents. The simplest account is the identity function, which equates subjective and objective opportunity costs. A variant of this function called the "sigmoidal-slope function," converges on the identity function at longer durations but deviates from it at shorter durations. The sigmoidal-slope function has the form of a hockey stick. The flat "blade" denotes a range over which opportunity costs are subjectively equivalent; these durations are too short to allow substitution of more beneficial activities. The blade extends into an upward-curving portion over which costs become discriminable and finally into the straight "handle," over which objective and subjective costs match. The two remaining functions are based on hyperbolic and exponential temporal discounting, respectively. The results are best described by the sigmoidal-slope function. That this is so suggests that different principles of intertemporal choice are involved in the evaluation of time spent working for a reward or waiting for its delivery. The subjective opportunity-cost function plays a key role in the evaluation and selection of goals. An accurate description of its form and parameters is essential to successful modeling and prediction of instrumental performance and reward-related decision making.

Project description:IntroductionTobacco is highly addictive, and after the development of dependence, it is difficult to quit smoking. Therefore, it is important to understand the factors that play a role in the initiation of smoking. The rewarding effects of nicotine play a role in the initiation of smoking and the goal of the present study was to determine the rewarding effects of nicotine in adolescent and adult male and female rats.MethodsMale and female Wistar rats were prepared with intracranial self-stimulation (ICSS) electrodes between postnatal day (P) 23 and 33. They were then trained on the ICSS procedure and the effect of nicotine (0, 0.03, 0.1, 0.3 mg/kg) on the reward thresholds and response latencies was investigated during adolescence (P40-59) or adulthood (>P75).ResultsNicotine lowered the brain reward thresholds of the adult and adolescent male and female rats. The nicotine-induced decrease in the reward thresholds was the same in the adult male and adult female rats. However, nicotine induced a greater decrease in the reward thresholds of the adolescent female rats than the adolescent male rats. Nicotine decreased the response latencies of all groups and there was no effect of age or sex.ConclusionsNicotine enhances reward function and psychomotor performance in adolescent and adult male and female rats. Adolescent female rats are more sensitive to the acute rewarding effects of nicotine than adolescent male rats. Therefore, the rewarding effects of nicotine might play a greater role in the initiation of smoking in adolescent females than in adolescent males.ImplicationsThe great majority of people start smoking during adolescence. The present studies suggest that during this period female rats are more sensitive to the acute rewarding effects of low and intermediate doses of nicotine than male rats. The rewarding properties of nicotine play a role in the initiation of smoking and establishing habitual smoking. Therefore, the present findings might explain why adolescent females are at a higher risk for becoming nicotine dependent than adolescent males.

Project description:BackgroundDepression is a neurological disorder characterized by persistent low mood. A number of studies have suggested that the use of type 1 cannabinoid receptor (CB1R) agonists can reduce depressive behavior, but its effect on the depressive behavior and nerve damage of rats exposed to chronic unpredictable mild stress (CUMS) has not been reported.MethodsRats were exposed to CUMS for 4 weeks to induce depressive behavior. Male Sprague-Dawley (SD) rats aged 6-8 weeks were randomly divided into six groups: control group (control), depression group (CUMS), depression + fluoxetine group (Flu), depression + WIN55212-2 group (WIN), depression + NF-κB inhibitor group (PDTC), and depression + WIN + PDTC group (WIN + PDTC). We performed four behavioral experiments test to evaluate the depressive behaviors of rats. Hematoxylin and eosin (HE) and Nissl staining were performed to observe the neuron structures of the hippocampus. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2). Biochemical experiments were performed to evaluate the concentrations of nitric oxide (NO), malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD). Fluorescence quantitative PCR was used to detect the mRNA expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), and inducible nitric oxide synthase (iNOS) in the hippocampus, and western blot was performed to detect protein expression levels related to the NF-κB signaling pathway in the hippocampus.ResultsCompared with the normal control group, CUMS significantly induced abnormal behaviors in stressed rats. The concentrations of pro-inflammatory factors and oxidative stress injury factors in the hippocampus of the CUMS group increased significantly. The interventions of Flu, WIN, and PDTC significantly reduced neuroinflammation and oxidative stress injury. Compared with the WIN group, the WIN + PDTC intervention group had better results. In addition, WIN could significantly inhibit the activation of the NF-κB signaling pathway.ConclusionsThis study showed that cannabinoid receptor agonists can reduce the CUMS-induced depressive behaviors of rats by blocking the NF-κB signaling pathway to alleviate neuroinflammation and oxidative stress injury.

Dataset Information

Cannabinoid receptor blockade reduces the opportunity cost at which rats maintain operant performance for rewarding brain stimulation.

Publications

Cannabinoid receptor blockade reduces the opportunity cost at which rats maintain operant performance for rewarding brain stimulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets