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Maryna Koskela, T Petteri Piepponen, Jaan-Olle Andressoo, Vootele Võikar, Mikko Airavaara
It is about half a century ago when the so-called "Wise model" to study alcohol drinking behavior in rats was established. The model was based on voluntary intermittent access to increasing concentrations of alcohol. We aimed to establish a model of alcohol craving and used an extinction test on withdrawal days 1 and 10 to study motivation for alcohol. For this purpose, the alcohol drinking training was paired with light cues to establish conditioning. The extinction test was carried out without alcohol but in the presence of light cues and empty bottles...
March 20, 2018: Behavioural Brain Research
Sarah Fischbach-Weiss, Rebecca M Reese, Patricia H Janak
Mesolimbic dopamine perturbations modulate performance of reward-seeking behavior, with tasks requiring high effort being especially vulnerable to disruption of dopamine signaling. Previous work primarily investigated long-term perturbations such as receptor antagonism and dopamine depletion, which constrain the ability to assess dopamine contributions to effort expenditure in isolation from other behavior events, such as reward consumption. Also unclear is if dopamine is required for both initiation and maintenance when a sequence of multiple instrumental responses is required...
February 21, 2018: Neuroscience
Péter Pelsőczi, György Lévay
Automated homecage monitoring systems are now widely recognized and used tools in cognitive neuroscience. However, few of these studies cover pharmacological interventions. Scopolamine, an anticholinergic memory disrupting agent is frequently used to study learning behavior. We studied the impact of scopolamine treatment in a relevant dose-range on activity, drinking behavior and reversal learning of C57BL/DJ mice in a homecage-like, social environment, using the IntelliCage. Naïve mice were first habituated to the IntelliCage, where they learned to nosepoke in any of the four corners in order to gain access to the water reward...
December 2017: Neurochemical Research
Hua Tang, Xuan Sun, Bao-Ming Li, Fei Luo
Decision making refers to the process that subjects use to choose between competing courses of action based on the expected costs and benefits of their consequences. However, few studies have addressed the neuronal mechanisms behind the processes of how costs and benefits influence decision making. Here we investigated the neuronal representation of costs and benefits towards a goal-directed action under a differential reward schedule by training rats to perform a "Do more, get more" (DM-GM) task utilizing a nosepoke operandum, where longer nosepoke durations resulted in correspondingly larger rewards...
November 1, 2017: Neuroscience Letters
Janaina C M Vendruscolo, Brendan J Tunstall, Stephanie A Carmack, Brooke E Schmeichel, Emily G Lowery-Gionta, Maury Cole, Olivier George, Sophia A Vandewater, Michael A Taffe, George F Koob, Leandro F Vendruscolo
Opioid misuse is at historically high levels in the United States, with inhalation (ie, smoking and vaping) being one of the most common routes of consumption. We developed and validated a novel preclinical model of opioid self-administration by inhalation that does not require surgery and reliably produces somatic and motivational signs of dependence. Rats were trained to perform an operant response (nosepoke) to receive 10 s of vaporized sufentanil, a potent opioid, in 2 h daily sessions. Rats readily and concentration-dependently self-administered vaporized sufentanil...
March 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Shelley M Warlow, Mike J F Robinson, Kent C Berridge
Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation...
August 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Julia Schroeder, Dennis Garlick, Aaron P Blaisdell
A series of experiments illustrated the effectiveness and flexibility of a newly developed Automated Remote Environmental Navigation Apparatus (ARENA) as an alternative to traditional operant and open-field procedures. This system improves the concept developed by Badelt and Blaisdell (Behavior Research Methods, 40, 613-621, 2008; see also Leising, Garlick, Parenteau, & Blaisdell in Behavioural Processes, 81, 105-113, 2009), with significant upgrades in flexibility and reliability, as well as a reduction in cost...
June 2, 2017: Behavior Research Methods
Giordano de Guglielmo, Marsida Kallupi, Maury D Cole, Olivier George
RATIONALE: A major issue in the addiction field is the limited number of animal models of the voluntary induction and maintenance of alcohol dependence in outbred rats. OBJECTIVES: To address this issue, we developed a novel apparatus that vaporizes alcohol for 2-10 min after an active nosepoke response. METHODS: Male Wistar rats were allowed to self-administer alcohol vapor for 8 h/day every other day for 24 sessions (escalated) or eight sessions (non-escalated)...
July 2017: Psychopharmacology
Kazuhiro Goto, Isao Ito
Left-right (L-R) asymmetry is a fundamental feature of brain function, but the mechanisms underlying functional asymmetry remain largely unknown. We previously identified structural and functional asymmetries in the circuitry of the mouse hippocampus that result from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B) subunits. By examining the synaptic distribution of ε2 subunits, we found that β2-microglobulin (β2m)-deficient mice that are defective in the stable cell surface expression of major histocompatibility complex class I (MHCI) lack this circuit asymmetry...
March 2017: Neurobiology of Learning and Memory
Shuai Wang, Yi Shi, Bao-Ming Li
The anterior cingulate cortex (ACC) is crucial for decision making which involves the processing of cost-benefit information. Our previous study has shown that ACC is essential for self-paced decision making. However, it is unclear how ACC neurons represent cost-benefit selections during the decision-making process. In the present study, we trained rats on the same "Do More Get More" (DMGM) task as in our previous work. In each trial, the animals stand upright and perform a sustained nosepoke of their own will to earn a water reward, with the amount of reward positively correlated to the duration of the nosepoke (i...
March 2017: Neurobiology of Learning and Memory
Lay Khoon Too, Kong M Li, Cacang Suarna, Ghassan J Maghzal, Roland Stocker, Iain S McGregor, Nicholas H Hunt
This article demonstrates behavioral changes in mice in response to free adaptation and drinking session adaptation modules implemented in their social home environment, the IntelliCage. These data complement the study "Deletion of TDO2, IDO-1 and IDO-2 differentially affects mouse behavior and cognitive function" (Too LK, Li KM, Suarna C, Maghzal GJ, Stocker R, McGregor IS, et al., 2016) [1]. Prior to programmed drinking sessions, all mice were exposed to a home cage adaptation module during which there was no time limit on water access - the free adaptation module...
December 2016: Data in Brief
Shuai Wang, Shan-Hu Hu, Yi Shi, Bao-Ming Li
It has been shown that the anterior cingulate cortex (ACC) and its dopamine system are crucial for decision making that requires physical/emotional effort, but not for all forms of cost-benefit decision making. Previous studies had mostly employed behavioral tasks with two competing cost-reward options that were preset by the experimenters. However, few studies have been conducted using scenarios in which the subjects have full control over the energy/time expenditure required to obtain a proportional reward...
March 2017: Learning & Behavior
Hua Tang, Fei Luo, Si-Hai Li, Bao-Ming Li
Decision making is dependent upon individual motivation. Previous studies showed that animals with higher levels of motivation are more likely to invest more time to acquire larger rewards rather than acquiring smaller rewards with less time to wait. However, little is known about how this motivation mediates the cognitive effort animals devote upon making said decisions in detail. In the present study, we investigated the behavioral response in a goal-directed action under a differential reward schedule by training rats to perform a "Do more, get more" (DM-GM) task using a nosepoke operandum when longer nosepoke durations resulted in correspondingly larger rewards...
October 6, 2016: Neuroscience Letters
Lay Khoon Too, Iain S McGregor, Alan G Baxter, Nicholas H Hunt
Activation of the immune system due to infection or aging is increasingly linked to impaired neuropsychological function. Toll-like receptors 2 and 4 (TLR2, TLR4) are well-characterised for their role in inflammatory events, and their combined activation has been implicated in neurological diseases. We therefore determined whether TLR2 and TLR4 double gene knockout (GKO) mice showed modified behaviour and cognitive function during a 16-day test sequence that employed the automated IntelliCage test system. The IntelliCage features a home cage environment in which groups of mice live and where water reward is gained through performing various tasks centred on drinking stations in each corner of the apparatus...
April 15, 2016: Behavioural Brain Research
Rachel L Schassburger, Emily M Pitzer, Tracy T Smith, Laura E Rupprecht, Edda Thiels, Eric C Donny, Alan F Sved
INTRODUCTION: Although nearly 90% of current smokers initiated tobacco use during adolescence, little is known about reinforcement by nicotine in adolescents. Researchers are currently investigating whether a potential public health policy setting a tobacco product standard with very low nicotine levels would improve public health, and it is essential to understand whether data generated in adults translates to adolescents, particularly as it relates to the threshold dose of nicotine required to support smoking...
September 2016: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
Leigh V Panlilio, Eric B Thorndike, Spyros P Nikas, Shakiru O Alapafuja, Tiziano Bandiera, Benjamin F Cravatt, Alexandros Makriyannis, Daniele Piomelli, Steven R Goldberg, Zuzana Justinova
RATIONALE: Manipulations of the endocannabinoid system could potentially produce therapeutic effects with minimal risk of adverse cannabis-like side effects. Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of the cannabinoid-receptor agonist, anandamide, and show promise for treating a wide range of disorders. However, their effects on learning and memory have not been fully characterized. OBJECTIVES: We determined the effects of five structurally different FAAH inhibitors in an animal model of working memory known to be sensitive to impairment by delta-9 tetrahydrocannabinol (THC)...
May 2016: Psychopharmacology
Benjamin J De Corte, Matthew S Matell
Rats trained on a dual-duration, dual-modality peak-interval procedure (e.g., tone = 10 s/light = 20 s) often show unimodal response distributions with peaks that fall in between the anchor durations when both cues are presented as a simultaneous compound. Two hypotheses can explain this finding. According to the averaging hypothesis, rats integrate the anchor durations into an average during compound trials, with each duration being weighted by its respective reinforcement probability. According to the simultaneous temporal processing hypothesis, rats time both durations veridically and simultaneously during compound trials and respond continuously across both durations, thereby producing a unimodal response distribution with a peak falling in between the anchor durations...
March 2016: Animal Cognition
Yan Zhang, Yanxue Xue, Shiqiu Meng, Yixiao Luo, Jie Liang, Jiali Li, Sizhi Ai, Chengyu Sun, Haowei Shen, Weili Zhu, Ping Wu, Lin Lu, Jie Shi
BACKGROUND: Drug memories that associate drug-paired stimuli with the effects of abused drugs contribute to relapse. Exposure to drug-associated contexts causes consolidated drug memories to be in a labile state, during which manipulations can be given to impair drug memories. Although substantial evidence demonstrates the crucial role of neuronal signaling in addiction, little is known about the contribution of astrocyte-neuron communication. METHODS: Rats were trained for cocaine-induced conditioned place preference (CPP) or self-administration and microinjected with the glycogen phosphorylation inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol into the basolateral amygdala (BLA) immediately after retrieval...
June 1, 2016: Biological Psychiatry
Hai-Shui Shi, Yi-Xiao Luo, Xi Yin, Hong-Hai Wu, Gai Xue, Xu-Hong Geng, Yan-Ning Hou
Drug addiction is considered an aberrant form of learning, and drug-associated memories evoked by the presence of associated stimuli (drug context or drug-related cues) contribute to recurrent craving and reinstatement. Epigenetic changes mediated by DNA methyltransferase (DNMT) have been implicated in the reconsolidation of fear memory. Here, we investigated the role of DNMT activity in the reconsolidation of cocaine-associated memories. Rats were trained over 10 days to intravenously self-administer cocaine by nosepokes...
2015: Scientific Reports
R J Wickham, W B Solecki, E J Nunes, N A Addy
Stimuli paired with rewards acquire reinforcing properties to promote reward-seeking behavior. Previous work supports the role of ventral tegmental area (VTA) nicotinic acetylcholine receptors (nAChRs) in mediating conditioned reinforcement elicited by drug-associated cues. However, it is not known whether these cholinergic mechanisms are specific to drug-associated cues or whether VTA cholinergic mechanisms also underlie the ability of cues paired with natural rewards to act as conditioned reinforcers. Burst firing of VTA dopamine (DA) neurons and the subsequent phasic DA release in the nucleus accumbens (NAc) plays an important role in cue-mediated behavior and in the ability of cues to acquire reinforcing properties...
August 20, 2015: Neuroscience
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