Initiation and maintenance of oral ethanol self-administration in female Sprague-Dawley rats

Background: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. Aim: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. Methods: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62–82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. Results: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. Conclusions: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.

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The vagus nerve mediates the suppressing effects of peripherally administered oxytocin on methamphetamine self-administration and seeking in rats

10.1101/2019.12.18.880914 ◽

2019 ◽

Author(s):

Nicholas A. Everett ◽

Anita J Turner ◽

Priscila A Costa ◽

Sarah J. Baracz ◽

Jennifer L. Cornish

Keyword(s):

Clinical Trials ◽

Vagus Nerve ◽

Drug Withdrawal ◽

Sham Operation ◽

Sprague Dawley ◽

Self Administration ◽

Male And Female ◽

Functional Interactions ◽

Sprague Dawley Rats ◽

Suppressant Effect

AbstractBackgroundThe neuropeptide oxytocin has emerged as a promising pharmacotherapy for methamphetamine (METH) addiction, and clinical trials of intranasal oxytocin are underway. However, there is debate as to how peripherally administered oxytocin alters brain signaling to modulate addiction processes. Interestingly, there is evidence for functional interactions between peripheral oxytocin administration and the vagus nerve. Therefore, this study investigated whether the effects of peripherally administered oxytocin require vagal signaling to reduce METH self-administration and reinstatement of METH-seeking behaviours.MethodsMale and female Sprague-Dawley rats underwent surgery for jugular catheterization and either subdiaphragmatic vagotomy (SDV) or a sham operation. Rats were trained to self-administer METH, and the effect of peripherally administered oxytocin on METH intake was assessed. Rats then underwent extinction, and effects of oxytocin were assessed on cue- and METH-induced reinstatement of METH-seeking.ResultsOxytocin treatment robustly attenuated METH intake in both sexes. Strikingly, SDV entirely prevented the suppressant effect of oxytocin (0.3 mg/kg) on METH intake, and partially prevented the effects of 1 mg/kg oxytocin in both sexes. After extinction, SDV impaired the suppressing effects of oxytocin on cue- and METH-primed reinstatement in males, but not females. SDV was functionally confirmed by measuring food intake following administration of the vagal dependent peptide, cholecyostokin-8.ConclusionOur data suggest that vagus nerve signaling is required for the anti-addiction effects of peripherally administered oxytocin, and that this vagal dependency is partially mediated by sex and drug withdrawal. This study has considerable implications for the applicability of oxytocin as a therapy for METH use disorder for both sexes.

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7,8-Dihydroxyflavone Enhances Cue-Conditioned Alcohol Reinstatement in Rats

Brain Sciences ◽

10.3390/brainsci10050270 ◽

2020 ◽

Vol 10 (5) ◽

pp. 270 ◽

Cited By ~ 1

Author(s):

Samuel J. Hogarth ◽

Elvan Djouma ◽

Maarten van den Buuse

Keyword(s):

Body Weight ◽

Progressive Ratio ◽

Ethanol Exposure ◽

Ethanol Solution ◽

Female Rats ◽

Male Rats ◽

Sprague Dawley ◽

Self Administration ◽

Bdnf Expression ◽

Sprague Dawley Rats

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.

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Correction to: Analysis of neurotransmitter levels in addiction-related brain regions during synthetic cathinone self-administration in male Sprague-Dawley rats

Psychopharmacology ◽

10.1007/s00213-019-05266-4 ◽

2019 ◽

Vol 236 (4) ◽

pp. 1405-1406

Author(s):

Julie A. Marusich ◽

Elaine A. Gay ◽

Bruce E. Blough

Keyword(s):

Brain Regions ◽

Sprague Dawley ◽

Self Administration ◽

Sprague Dawley Rats ◽

Synthetic Cathinone

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Electroacupuncture Suppresses Discrete Cue-Evoked Heroin-Seeking and Fos Protein Expression in the Nucleus Accumbens Core in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/286404 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Sheng Liu ◽

Fenglei Zhu ◽

Miaojun Lai ◽

Limin Sun ◽

Yijun Liu ◽

...

Keyword(s):

Nucleus Accumbens ◽

Therapeutic Benefit ◽

Sprague Dawley ◽

Contextual Cues ◽

Self Administration ◽

Nucleus Accumbens Core ◽

Beneficial Effects ◽

Fos Protein ◽

Sprague Dawley Rats ◽

Seeking Behavior

Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. Here, we used intravenous drug self-administration procedures in rats to further investigate the beneficial effects of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of relapse. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4 h or 25 infusions for 14 consecutive days. Then the rats were abstinent from heroin for two weeks. 2 Hz EA stimulation was conducted once daily for 14 days during heroin abstinence. We tested these animals for contextual and discrete cue-induced reinstatement of active responses. We also applied immunohistochemistry to detect Fos-positive nuclei in the nucleus accumbens (NACc) core and shell after reinstatement test. We found that active responses elicited by both contextual cues and discrete cues were high in the rats trained with heroin than in saline controls. EA treatment significantly reduced active responses elicited by discrete cues. EA stimulation attenuated Fos expression in the core but not the shell of the NACc. Altogether, these results highlight the therapeutic benefit of EA in preventing relapse to drug addiction.

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