scholarly journals Post-weaning social isolation modulates reward-seeking behavior in a sex-specific manner in mice

2021 ◽  
Author(s):  
Michael Noback ◽  
James C Barrow ◽  
Gregory V Carr
Keyword(s):  
Social Isolation ◽  
Performance Test ◽  
Fixed Ratio ◽  
Reaction Times ◽  
Progressive Ratio ◽  
Behavioral Model ◽  
Critical Periods ◽  
Schedules Of Reinforcement ◽  
Reward Seeking ◽  
Seeking Behavior

Social isolation is a growing concern in public health. Although isolation at any age is harmful, previous studies have shown that isolation during adolescence, correlating with critical periods of brain development, can impair cognitive function and increase the risk for psychiatric illness later in life. In this study, we utilized a mouse model of adolescent social isolation (SI) and compared performance of isolated and group-housed mice on a touchscreen-based continuous performance test (CPT) and fixed ratio/progressive ratio (FR/PR) tasks in adulthood. SI increased sensitivity in the CPT in male mice and had no effect in female mice. The increase in sensitivity was consistent across time bins within the 45-minute testing session and there were no SI effects on reaction times or reward retrieval latencies. A possible confound for performance in the CPT would be SI-induced changes in reward-seeking or motivation for the strawberry milk reward. We next compared the SI mice to their group-housed littermate controls on both FR and PR schedules of reinforcement and found that male SI mice earned significantly more reinforcers on FR schedules of reinforcement and had higher breakpoints on PR schedules compared to their group-housed littermates. These data indicate that SI during adolescence has striking, sex-specific effects on reward-seeking behavior in adult mice and may provide a useful behavioral model for studying the link between SI and risk for neuropsychiatric disorders.

The dopamine β-hydroxylase inhibitor, nepicastat, suppresses chocolate self-administration and reinstatement of chocolate seeking in rats

2013 ◽  
Vol 110 (8) ◽  
pp. 1524-1533 ◽  
Author(s):  
Alessandro Zaru ◽  
Paola Maccioni ◽  
Giancarlo Colombo ◽  
Gian Luigi Gessa
Keyword(s):  
Fixed Ratio ◽  
Progressive Ratio ◽  
Schedules Of Reinforcement ◽  
Self Administration ◽  
Pharmacological Agents ◽  
New Class ◽  
Cocaine Seeking ◽  
Reinforcement Measures ◽  
Food Seeking ◽  
Prevention Of Relapse

Craving for chocolate is a common phenomenon, which may evolve to an addictive-like behaviour and contribute to obesity. Nepicastat is a selective dopamine β-hydroxylase (DBH) inhibitor that suppresses cocaine-primed reinstatement of cocaine seeking in rats. We verified whether nepicastat was able to modify the reinforcing and motivational properties of a chocolate solution and to prevent the reinstatement of chocolate seeking in rats. Nepicastat (25, 50 and 100 mg/kg, intraperitoneal) produced a dose-related inhibition of operant self-administration of the chocolate solution in rats under fixed-ratio 10 (FR10) and progressive-ratio schedules of reinforcement, measures of the reinforcing and motivational properties of the chocolate solution, respectively. The effect of nepicastat on the reinstatement of chocolate seeking was studied in rats in which lever-responding had been extinguished by removing the chocolate solution for approximately 8 d. Nepicastat dose-dependently suppressed the reinstatement of lever-responding triggered by a ‘priming’ of the chocolate solution together with cues previously associated with the availability of the reward. In a separate group of food-restricted rats trained to lever-respond for regular food pellets, nepicastat reduced FR10 lever-responding with the same potency as for the chocolate solution. Spontaneous locomotor activity was not modified by nepicastat doses that reduced self-administration of the chocolate solution and regular food pellets and suppressed the reinstatement of chocolate seeking. The results indicate that nepicastat reduces motivation to food consumption sustained by appetite or palatability. Moreover, the results suggest that DBH inhibitors may be a new class of pharmacological agents potentially useful in the prevention of relapse to food seeking in human dieters.

scholarly journals Knockdown of Hypocretin/Orexin Attenuates Extended-Access Cocaine Self-Administration in Rats

2017 ◽  
Author(s):  
Brooke E. Schmeichel ◽  
Alessandra Matzeu ◽  
Pascale Koebel ◽  
Leandro F. Vendruscolo ◽  
Brigitte L. Kieffer ◽  
...  
Keyword(s):  
Stress Responses ◽  
Viral Vector ◽  
Fixed Ratio ◽  
Progressive Ratio ◽  
Ratio Schedule ◽  
Self Administration ◽  
Adult Rats ◽  
Extended Access ◽  
Seeking Behavior ◽  
Melanin Concentrating Hormone

AbstractThe hypocretin/orexin (HCRT) neuropeptide system regulates feeding, arousal state, stress responses, and reward, especially under conditions of enhanced motivational relevance. In particular, HCRT neurotransmission facilitates drug-seeking behavior in circumstances that demand increased effort and/or motivation to take the drug. The present study used a shRNA-encoding adeno-associated viral vector to knockdown Hcrt expression throughout the dorsal hypothalamus in adult rats and determine the role of HCRT in cocaine self-administration. Longterm Hcrt silencing did not impact cocaine self-administration under short-access conditions, but robustly attenuated cocaine intake during extended self-administration access, a model that mimics key features of compulsive cocaine-taking. In addition, Hcrt silencing decreased motivation for both cocaine and palatable food (i.e., sweetened condensed milk; SCM) under a progressive ratio schedule of reinforcement, but did not alter responding for SCM under a fixed ratio schedule. Importantly, Hcrt silencing did not affect food or water consumption, and had no consequence to general measures of arousal-dependent behaviors. At the molecular level, longterm Hcrt knockdown moderately reduced the downstream expression of dynorphin (DYN) and melanin-concentrating hormone (MCH) in the dorsal hypothalamus. These original findings support the hypothesis that HCRT neurotransmission promotes operant responding for both drug and non-drug rewards, preferentially under conditions requiring a high degree of motivation. Furthermore, the current study provides compelling evidence for the involvement of the HCRT system in cocaine self-administration also under low-effort conditions in rats allowed extended access, possibly via functional interactions with DYN and MCH signaling.

scholarly journals The Novel Positive Allosteric Modulator of the GABAB Receptor, KK-92A, Suppresses Alcohol Self-Administration and Cue-Induced Reinstatement of Alcohol Seeking in Rats

2021 ◽  
Vol 9 ◽  
Author(s):  
Paola Maccioni ◽  
Katarzyna Kaczanowska ◽  
Harshani Lawrence ◽  
Sang Yun ◽  
Jessica Bratzu ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Drugs Of Abuse ◽  
Gabab Receptor ◽  
Fixed Ratio ◽  
Progressive Ratio ◽  
Spontaneous Locomotor Activity ◽  
Schedules Of Reinforcement ◽  
Self Administration ◽  
Motivated Behaviors ◽  
Alcohol Seeking

Positive allosteric modulators (PAMs) of the GABAB receptor (GABAB PAMs) are of interest in the addiction field due to their ability to suppress several behaviors motivated by drugs of abuse. KK-92A is a novel GABAB PAM found to attenuate intravenous self-administration of nicotine and reinstatement of nicotine seeking in rats. This present study was aimed at extending to alcohol the anti-addictive properties of KK-92A. To this end, Sardinian alcohol-preferring rats were trained to lever-respond for oral alcohol (15% v/v) or sucrose (0.7% w/v) under the fixed ratio (FR) 5 (FR5) schedule of reinforcement. Once lever-responding behavior had stabilized, rats were exposed to tests with acutely administered KK-92A under FR5 and progressive ratio schedules of reinforcement and cue-induced reinstatement of previously extinguished alcohol seeking. KK-92A effect on spontaneous locomotor activity was also evaluated. Treatment with 10 and 20 mg/kg KK-92A suppressed lever-responding for alcohol, amount of self-administered alcohol, and breakpoint for alcohol. Treatment with 20 mg/kg KK-92A reduced sucrose self-administration. Combination of per se ineffective doses of KK-92A (2.5 mg/kg) and the GABAB receptor agonist, baclofen (1 mg/kg), reduced alcohol self-administration. Treatment with 5, 10, and 20 mg/kg KK-92A suppressed reinstatement of alcohol seeking. Only treatment with 80 mg/kg KK-92A affected spontaneous locomotor activity. These results demonstrate the ability of KK-92A to inhibit alcohol-motivated behaviors in rodents and confirm that these effects are common to the entire class of GABAB PAMs. The remarkable efficacy of KK-92A is discussed in terms of its ago-allosteric properties.

scholarly journals Assessment of Demand for Food using Concurrent PR and FR Schedules in the Brushtail Possum (Trichosurus vulpecula)

2015 ◽  
Vol 28 ◽  
Author(s):  
Kristie E. Cameron ◽  
Lewis A. Bizo ◽  
Nicola J. Starkey
Keyword(s):  
Fixed Ratio ◽  
Food Preferences ◽  
Progressive Ratio ◽  
Food Sources ◽  
Ratio Schedule ◽  
Brushtail Possum ◽  
Progressive Ratio Schedule ◽  
Schedules Of Reinforcement ◽  
Cross Point ◽  
Consumption Rates

The aim of this study was to compare the demand by possums for foods under different arrangements of concurrent progressive-ratio and fixed-ratio schedules of reinforcement. In Experiment 1, every possible food pair made up of berries, chicken, egg, foliage, insects and mushroom was presented (30 pairs in total). The requirement on the progressive-ratio schedule increased within a session and the fixed-ratio was kept constant at 30. In Experiment 2, a subset of the foods from Experiment 1 were used (chicken, mushroom, egg and berries) and in separate conditions the fixed-ratio was either 30 or 10 responses. In Experiment 3, the foods were the same as used in Experiment 2 and the progressive-ratio schedule increased every five sessions and the fixed-ratio schedule was 30 responses. Exponential models of demand were applied to consumption rates to compare the parameters of initial demand, essential value and P max, and break point and cross point across foods. The models described the data well and consumption rates were similar when the incrementing schedules increased within- and across sessions. Demand was highest for berries, egg and locust in Experiment 1 and egg and chicken in Experiments 2 and 3. This finding has practical implications for understanding possum food preferences in the wild as a function of other available food sources.

scholarly journals Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

2019 ◽  
Author(s):  
Timothy G. Freels ◽  
Lydia N. Baxter-Potter ◽  
Janelle M. Lugo ◽  
Nicholas C. Glodosky ◽  
Hayden R. Wright ◽  
...  
Keyword(s):  
Fixed Ratio ◽  
Progressive Ratio ◽  
Sprague Dawley ◽  
Self Administration ◽  
Daily Food ◽  
Sprague Dawley Rats ◽  
Seeking Behavior ◽  
Break Points ◽  
Bona Fide ◽  
Novel Method

ABSTRACTRecent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug employed and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized Δ9-tetrahydrocannabinol-rich (CANTHC) or cannabidiol-rich (CANCBD) complete cannabis extracts. Male Sprague Dawley rats were trained to nosepoke for discrete puffs of CANTHC, CANCBD, or vehicle (VEH) in daily one-hour sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CANTHC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared to CANCBD or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CANTHC administration decreased hippocampal CB1 receptor binding. Removal of CANTHC reinforcement (but not CANCBD) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors.

scholarly journals The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents

2020 ◽  
Vol 21 (13) ◽  
pp. 4631
Author(s):  
In Soo Ryu ◽  
Oc-Hee Kim ◽  
Young Eun Lee ◽  
Ji Sun Kim ◽  
Zhan-Hui Li ◽  
...  
Keyword(s):  
Intraperitoneal Administration ◽  
Fixed Ratio ◽  
Progressive Ratio ◽  
D1 Receptor ◽  
Abuse Potential ◽  
Signaling Cascades ◽  
Schedules Of Reinforcement ◽  
Self Administration ◽  
Downstream Signaling ◽  
Related Proteins

The dissociative anesthetic phencyclidine (PCP) and PCP derivatives, including 4′-F-PCP, are illegally sold and abused worldwide for recreational and non-medical uses. The psychopharmacological properties and abuse potential of 4′-F-PCP have not been fully characterized. In this study, we evaluated the psychomotor, rewarding, and reinforcing properties of 4′-F-PCP using the open-field test, conditioned place preference (CPP), and self-administration paradigms in rodents. Using Western immunoblotting, we also investigated the expression of dopamine (DA)-related proteins and DA-receptor-mediated downstream signaling cascades in the nucleus accumbens (NAc) of 4′-F-PCP-self-administering rats. Intraperitoneal administration of 10 mg/kg 4′-F-PCP significantly increased locomotor and rearing activities and increased CPP in mice. Intravenous administration of 1.0 mg/kg/infusion of 4′-F-PCP significantly enhanced self-administration during a 2 h session under fixed ratio schedules, showed a higher breakpoint during a 6 h session under progressive ratio schedules of reinforcement, and significantly altered the expression of DA transporter and DA D1 receptor in the NAc of rats self-administering 1.0 mg/kg 4′-F-PCP. Additionally, the expression of phosphorylated (p) ERK, pCREB, c-Fos, and FosB/ΔFosB in the NAc was significantly enhanced by 1.0 mg/kg 4′-F-PCP self-administration. Taken together, these findings suggest that 4′-F-PCP has a high potential for abuse, given its robust psychomotor, rewarding, and reinforcing properties via activation of DAergic neurotransmission and the downstream signaling pathways in the NAc.

Cannabidiol treatment reduces the motivation to self-administer methamphetamine and methamphetamine-primed relapse in rats

2018 ◽  
Vol 32 (12) ◽  
pp. 1369-1378 ◽  
Author(s):  
Gracie L Hay ◽  
Sarah J Baracz ◽  
Nicholas A Everett ◽  
Jessica Roberts ◽  
Priscila A Costa ◽  
...  
Keyword(s):  
Lever Press ◽  
Jugular Vein ◽  
Fixed Ratio ◽  
Progressive Ratio ◽  
Preliminary Evidence ◽  
Sprague Dawley ◽  
Psychosocial Effects ◽  
Methamphetamine Dependence ◽  
Sprague Dawley Rats ◽  
Seeking Behavior

Background: Methamphetamine is an addictive stimulant that can cause many adverse physical, psychological and psychosocial effects. Preliminary evidence shows cannabidiol, a non-intoxicating constituent of the cannabis plant, may have efficacy in treating opioid and nicotine dependence. However, no study has yet examined whether cannabidiol treatment might impact on methamphetamine addiction. Aims: The current study investigated whether cannabidiol administration reduces the motivation to self-administer methamphetamine and relapse to methamphetamine-seeking behavior following abstinence. Methods: Thirty-two male Sprague Dawley rats with implanted jugular vein catheters were initially trained to self-administer methamphetamine via lever press during two-hour sessions on a fixed ratio 1 schedule of reinforcement. Rats in experiment 1 ( n=16) then advanced to a progressive ratio reinforcement schedule to examine the effects of cannabidiol (0, 20, 40, and 80 mg/kg intraperitoneal) on motivation to self-administer methamphetamine. Rats in experiment 2 ( n=16) were tested for cannabidiol effects on methamphetamine-primed reinstatement following extinction. Results: Cannabidiol (80 mg/kg, but not 40 mg/kg, or 20 mg/kg) reduced the motivation to self-administer methamphetamine and attenuated methamphetamine-primed relapse to methamphetamine-seeking behavior after extinction. Conclusion: This is the first demonstration that cannabidiol can reduce the motivation to seek and consume methamphetamine, and suggests that cannabidiol might be worth trialing as a novel pharmacotherapy for methamphetamine dependence.

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