scholarly journals Role of anterior insula cortex in context-induced relapse of nicotine-seeking

2021 ◽  
Author(s):  
Hussein Ghareh ◽  
Isis Alonso-Lozares ◽  
Dustin Schetters ◽  
Rae J Herman ◽  
Tim S Heistek ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Critical Role ◽  
Insular Cortex ◽  
Female Rats ◽  
Negative Consequences ◽  
Self Administration ◽  
Retrograde Labelling ◽  
Male And Female Rats ◽  
Insula Cortex ◽  
Increased Activity

Tobacco use is the leading cause of preventable death worldwide, and relapse during abstinence remains the key barrier to successful treatment of tobacco addiction. During abstinence, environmental contexts associated with nicotine use can induce craving and contribute to relapse. The insular cortex (IC) is thought to be a critical substrate of nicotine addiction and relapse. However, its specific role in context-induced relapse of nicotine-seeking is not fully known. In this study, we report a novel rodent model of context-induced relapse to nicotine-seeking after punishment-imposed abstinence, which models self-imposed abstinence through increasing negative consequences of excessive drug use. Using the neuronal activity marker Fos we find that the anterior (aIC), but not the middle or posterior IC, shows increased activity during context-induced relapse. Combining Fos with retrograde labelling of aIC inputs, we show projections to aIC from contralateral aIC and basolateral amygdala exhibit increased activity during context-induced relapse. Next, we used fiber photometry in aIC and observed phasic increases in aIC activity around nicotine-seeking responses during self-administration, punishment, and the context-induced relapse tests. Next, we used chemogenetic inhibition in both male and female rats to determine whether activity in aIC is necessary for context-induced relapse. We found that chemogenetic inhibition of aIC decreased context-induced nicotine-seeking after either punishment- or extinction-imposed abstinence. These findings highlight the critical role nicotine-associated contexts play in promoting relapse, and they show that aIC activity is critical for this context-induced relapse following both punishment and extinction imposed abstinence.

scholarly journals Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Self Administration ◽  
Male And Female ◽  
Orexin Receptors ◽  
Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

Effect of cocaine self-administration on striatal PKA-regulated signaling in male and female rats

2006 ◽  
Vol 191 (2) ◽  
pp. 263-271 ◽  
Author(s):  
Wendy J. Lynch ◽  
Drew D. Kiraly ◽  
Barbara J. Caldarone ◽  
Marina R. Picciotto ◽  
Jane R. Taylor
Keyword(s):  
Female Rats ◽  
Self Administration ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Effects of nicotine exposure on oral methamphetamine self-administration, extinction, and drug-primed reinstatement in adolescent male and female rats

2020 ◽  
Vol 209 ◽  
pp. 107927 ◽  
Author(s):  
Zachary R. Harmony ◽  
Erin M. Alderson ◽  
Israel Garcia-Carachure ◽  
Laurence D. Bituin ◽  
Cynthia A. Crawford
Keyword(s):  
Female Rats ◽  
Adolescent Male ◽  
Nicotine Exposure ◽  
Self Administration ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Nicotine self-administration and reinstatement of nicotine-seeking in male and female rats

2012 ◽  
Vol 121 (3) ◽  
pp. 240-246 ◽  
Author(s):  
Matthew W. Feltenstein ◽  
Shannon M. Ghee ◽  
Ronald E. See
Keyword(s):  
Female Rats ◽  
Self Administration ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Assessing the effects of chronic sazetidine-A delivery on nicotine self-administration in both male and female rats

2012 ◽  
Vol 222 (2) ◽  
pp. 269-276 ◽  
Author(s):  
Joshua E. Johnson ◽  
Susan Slade ◽  
Corinne Wells ◽  
Ann Petro ◽  
Hannah Sexton ◽  
...  
Keyword(s):  
Female Rats ◽  
Self Administration ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Effects of Kappa Opioid Receptor Agonists on Fentanyl vs. Food Choice in Male and Female Rats: Contingent vs. Non-Contingent Administration

2020 ◽  
Author(s):  
E. Andrew Townsend
Keyword(s):  
Opioid Receptor ◽  
Food Choice ◽  
Food Reinforcement ◽  
Abuse Liability ◽  
Kappa Opioid Receptor ◽  
Female Rats ◽  
Self Administration ◽  
Kappa Opioid ◽  
Male And Female ◽  
Male And Female Rats

AbstractRationaleStrategies are needed to decrease the abuse liability of mu opioid receptor (MOR) agonists. One strategy under consideration is to combine MOR agonists with kappa opioid receptor (KOR) agonists.ObjectivesThe effects of KOR-agonists (U50488, nalfurafine) on fentanyl-versus-food choice were compared under conditions where the KOR agonists were added to the self-administered fentanyl (contingent delivery) or administered as pretreatments (non-contingent delivery) in male and female rats. The effects of increasing and decreasing the magnitude of the alternative food reinforcer were also determined.MethodsRats were trained to respond under a concurrent schedule of fentanyl (0, 0.32-10 μg/kg/infusion) and food reinforcement. In Experiment 1, U50488 and nalfurafine were co-administered with fentanyl as fixed-proportion mixtures (contingent administration). In Experiment 2, U50488 (1-10 mg/kg) and nalfurafine (3.2-32 μg/kg) were administered as acute pretreatments (non-contingent administration). nor-BNI (32 mg/kg) was administered prior to contingent and non-contingent KOR-agonist treatment in Experiment 3. Experiment 4 evaluated the effects of increasing and decreasing the magnitude of the non-drug reinforcer.ResultsBoth U50488 and nalfurafine decreased fentanyl choice when administered contingently, demonstrating that KOR agonists punish opioid choice. Non-contingent U50488 and nalfurafine administration decreased rates of fentanyl and food self-administration without altering fentanyl choice. Both contingent and non-contingent U50488 and nalfurafine effects on fentanyl choice were attenuated by nor-BNI. Fentanyl choice was sensitive to increases and decreases in the magnitude of the non-drug reinforcer.ConclusionsThese results demonstrate that the effects of KOR agonists on fentanyl reinforcement are dependent upon the contingencies under which they are administered.

scholarly journals Exploring sex differences in the prevention of ethanol drinking by naltrexone in dependent rats during abstinence

2018 ◽  
Author(s):  
A Matzeu ◽  
L Terenius ◽  
R Martin-Fardon
Keyword(s):  
Ethanol Withdrawal ◽  
Female Rats ◽  
Self Administration ◽  
Air Exposure ◽  
Male And Female ◽  
Motivational States ◽  
Male And Female Rats ◽  
The Central Nervous System ◽  
Males And Females ◽  
Time Of Intervention

AbstractBackgroundDespite considerable efforts, few drugs are available for the treatment of alcohol (ethanol [EtOH]) use disorders (AUDs). Ethanol directly or indirectly modulates several aspects of the central nervous system, including neurotransmitter/neuromodulator systems. Relapse vulnerability is a challenge for the treatment of EtOH addiction. Ethanol withdrawal symptoms create motivational states that lead to compulsive EtOH drinking and relapse even after long periods of abstinence. Among the therapeutics to treat AUDs, naltrexone (NTX) is a pharmacological treatment for relapse. The goal of the present study was to evaluate the effect of NTX on EtOH drinking in EtOH-dependent male and female rats during abstinence.MethodsWistar rats (males and females) were first trained to orally self-administer 10% EtOH. Half of them were then made dependent by chronic intermittent EtOH (CIE) vapor exposure, and the other half were exposed to air. Using this model, rats exhibit somatic and motivational signs of withdrawal. At the end of EtOH vapor (or air) exposure, the rats were tested for the effects of NTX (10 mg/kg, p.o.) on EtOH self-administration at three abstinence time points: acute abstinence (8 h, A-Abst), late abstinence (2 weeks, L-Abst), and protracted abstinence (6 weeks, P-Abst).ResultsNTX decreased EtOH intake in nondependent rats, regardless of sex and abstinence time point. In post-dependent rats, the effects of NTX improved with a longer abstinence time (i.e., L-Abst and P-Abst) in males, whereas it similarly reduced EtOH drinking in females at all abstinence points.ConclusionsThe data suggest that the therapeutic efficacy of NTX depends on the time of intervention during abstinence and sex. The data further suggest that EtOH dependence induces different neuroadaptations in male and female rats, reflected by differential effects of NTX. The results underscore the significance of considering the duration of EtOH abstinence and sex for the development of pharmacotherapeutic treatments for AUD.

scholarly journals Metformin in nucleus accumbens core reduces cue-induced cocaine seeking in male and female rats

2021 ◽  
Author(s):  
Amy Chan ◽  
Alexis Willard ◽  
Sarah Mulloy ◽  
Noor Ibrahim ◽  
Allegra Sciaccotta ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Female Rats ◽  
Therapeutic Effects ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking ◽  
Ampk Activity ◽  
Accumbens Core

This study investigated the potential therapeutic effects of the FDA-approved drug metformin on cue-induced reinstatement of cocaine seeking. Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK). Cocaine self-administration and extinction is associated with decreased levels of phosphorylated AMPK within the nucleus accumbens core (NAcore). Previously it was shown that increasing AMPK activity in the NAcore decreased cue-induced reinstatement of cocaine seeking. Decreasing AMPK activity produced the opposite effect. The goal of the present study was to determine if metformin in the NAcore reduces cue-induced cocaine seeking in adult male and female Sprague Dawley rats. Rats were trained to self-administer cocaine followed by extinction prior to cue-induced reinstatement trials. Metformin microinjected in the NAcore attenuated cue-induced reinstatement in male and female rats. Importantly, metformin's effects on cocaine seeking were not due to a general depression of spontaneous locomotor activity. In female rats, metformin's effects did generalize to a reduction in cue-induced reinstatement of sucrose seeking. These data support a potential role for metformin as a pharmacotherapy for cocaine use disorder, but warrant caution given the potential for metformin's effects to generalize to a natural reward in female rats.

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