scholarly journals Relapse-like behavior and nAChR sensitization following intermittent access nicotine self-administration

2022 ◽  
Author(s):  
Ryan Drenan ◽  
Xiao-Tao Jin ◽  
Brenton Tucker ◽  
Leanne Thomas ◽  
Noah Walker ◽  
...  
Keyword(s):  
Tobacco Consumption ◽  
Male Rats ◽  
Blood Levels ◽  
Self Administration ◽  
Interpeduncular Nucleus ◽  
Nicotine Intake ◽  
Positron Emission ◽  
Intermittent Access ◽  
Underlying Mechanisms ◽  
Incubation Of Craving

Many tobacco smokers consume nicotine intermittently, but the underlying mechanisms and neurobiological changes associated with intermittent nicotine intake are unclear. Understanding intermittent nicotine intake is a high priority, as it could promote therapeutic strategies to attenuate tobacco consumption. We examined nicotine intake behavior and neurobiological changes in male rats that were trained to self-administer nicotine during brief (5 min) trials interspersed with longer (15 min) drug-free periods. Rats readily adapted to intermittent access (IntA) SA following acquisition on a continuous access (ContA) schedule. Probabilistic analysis of IntA nicotine SA suggested reduced nicotine loading behavior compared to ContA, and nicotine pharmacokinetic modeling revealed that rats taking nicotine intermittently may have increased intake to maintain blood levels of nicotine that are comparable to ContA SA. After IntA nicotine SA, rats exhibited an increase in unreinforced responses for nicotine-associated cues (incubation of craving) and specific alterations in the striatal proteome after 7 days without nicotine. IntA nicotine SA also induced nAChR functional upregulation in the interpeduncular nucleus (IPN), and it enhanced nicotine binding in the brain as determined via [11C]nicotine positron emission tomography. Reducing the saliency of the cue conditions during the 5 min access periods attenuated nicotine intake, but incubation of craving was preserved. Together, these results indicate that IntA conditions promote nicotine SA and nicotine seeking after a nicotine-free period.

scholarly journals Taking rapid and intermittent cocaine infusions enhances both incentive motivation for the drug and cocaine-induced gene regulation in corticostriatal regions

2020 ◽  
Author(s):  
Ellie-Anna Minogianis ◽  
Anne-Noël Samaha
Keyword(s):  
Gene Regulation ◽  
Mrna Expression ◽  
Progressive Ratio ◽  
Incentive Motivation ◽  
Male Rats ◽  
Behavioural Plasticity ◽  
Self Administration ◽  
Drug Induced ◽  
Intermittent Access ◽  
Long Access

ABSTRACTA goal in addiction research is to distinguish forms of neuroplasticity that are involved in the transition to addiction from those involved in mere drug taking. Animal models of drug self-administration are essential in this context. Here, we compared in male rats two cocaine self-administration procedures that differ in the extent to which they evoke addiction-like behaviours. We measured both incentive motivation for cocaine using progressive ratio procedures, and cocaine-induced c-fos mRNA expression, a marker of neuronal activity. Rats self-administered intravenous cocaine (0.25 mg/kg/infusion) for seven daily 6-hour sessions. One group had intermittent access (IntA; 6 minutes ON, 26 minutes OFF x 12) to rapid infusions (delivered over 5 seconds). This models the temporal kinetics of human cocaine use and produces robust addiction-like behaviour. The other group had Long access (LgA) to slower infusions (90 seconds). This produces high levels of intake without promoting robust addiction-like behaviour. LgA-90s rats took twice as much cocaine as IntA-5s rats did, but IntA-5s rats showed greater incentive motivation for the drug. Following a final self-administration session, we quantified c-fos mRNA expression in corticostriatal regions. Compared to LgA-90s rats, IntA-5s rats had more cocaine-induced c-fos mRNA in the orbitofrontal and prelimbic cortices and the caudate-putamen. Thus, a cocaine self-administration procedure (intermittent intake of rapid infusions) that promotes increased incentive motivation for the drug also enhances cocaine-induced gene regulation in corticostriatal regions. This suggests that increased drug-induced recruitment of these regions could contribute to the neural and behavioural plasticity underlying the transition to addiction.

scholarly journals Nicotine Self-Administration With Tobacco Flavor Additives in Male Rats

2019 ◽  
Vol 22 (2) ◽  
pp. 224-231 ◽  
Author(s):  
Matthew I Palmatier ◽  
Amanda L Smith ◽  
Ethan M Odineal ◽  
Emily A Williams ◽  
Ashley B Sheppard ◽  
...  
Keyword(s):  
Ice Cream ◽  
Tobacco Consumption ◽  
Licorice Root ◽  
Male Rats ◽  
Root Extract ◽  
Self Administration ◽  
Neutral Group ◽  
Conditioned Reinforcers ◽  
Sweet Foods ◽  
Oral Presentations

Abstract Introduction Nicotine can robustly increase responding for conditioned reinforcers (CRs), stimuli that acquire reinforcing properties based on association with primary reinforcers. Menthol and licorice are tobacco flavoring agents also found in sweet foods (eg, candy and ice cream), making them putative CRs before they are consumed in tobacco. We sought to determine if intravenous self-administration (IVSA) of nicotine was enhanced by the inclusion of oral tobacco flavor CRs. Methods Menthol (160 or 320 µM) or licorice root extract (0.1% or 1%) were established as CRs (paired with 20% sucrose) or “neutral” stimuli (paired with water) in separate groups. During subsequent IVSA tests, nicotine was delivered in conjunction with oral presentations of the CR. Results In experiment 1, a menthol CR significantly shifted the peak nicotine dose from 15 µg/kg/infusion (Neutral group) to 3.25 µg/kg/infusion (CR group). In experiment 2, a menthol CR significantly increased operant licks for nicotine (3 µg/kg/infusion) relative to control groups. In experiment 3, both licorice and menthol CRs significantly increased operant licks for nicotine (7.5 µg/kg/infusion) relative to an “inactive” sipper. The licorice CR increased nicotine IVSA in proportion to the strength of the flavor, but both menthol concentrations increased nicotine IVSA to a similar extent. Conclusion Tobacco flavor additives with conditioned reinforcing properties promote acquisition of nicotine self-administration at low unit doses and may have robust impact on tobacco consumption when nicotine yield is low. Implications Tobacco flavor additives are found in rewarding foods (eg, ice cream) and gain palatability based on associations with primary rewards (eg, sugar) making them “conditioned reinforcers.” Nicotine increases the motivation for flavor conditioned reinforcers and the present studies show that tobacco flavor additives can interact with nicotine to promote more nicotine self-administration. The interaction between flavors additives and nicotine may promote nicotine exposure and subsequently dependence.

scholarly journals D-amphetamine maintenance therapy reduces cocaine use in female rats

2021 ◽  
Author(s):  
Ndeye Aissatou Ndiaye ◽  
Florence Allain ◽  
Anne-Noel Samaha
Keyword(s):  
Maintenance Therapy ◽  
Progressive Ratio ◽  
Cocaine Addiction ◽  
Female Rats ◽  
Male Rats ◽  
Ratio Schedule ◽  
Self Administration ◽  
Cocaine Use ◽  
Intermittent Access ◽  
Amphetamine Treatment

Currently, there are no approved medications to treat cocaine addiction. In this context, d-amphetamine maintenance therapy is a promising pharmacological strategy to reduce cocaine use. In both male rats and human cocaine users, d-amphetamine treatment reduces cocaine taking and seeking. However, this has not been examined systematically in female animals, even though cocaine addiction afflicts both women and men, and the sexes can differ in their response to cocaine. Here, we determined how d-amphetamine maintenance therapy during cocaine self-administration influences cocaine use in female rats. In experiment 1, two groups of female rats received 14 intermittent access (IntA) cocaine self-administration sessions. One group received concomitant d-amphetamine maintenance treatment (COC + A rats; 5 mg/kg/day, via minipump), the other group did not (COC rats) After discontinuing d-amphetamine treatment, we measured responding for cocaine under a progressive ratio schedule, responding under extinction and cocaine-primed reinstatement of drug seeking. In experiment 2, we assessed the effects of d-amphetamine maintenance on these measures in already cocaine-experienced rats. To this end, rats first received 14 IntA cocaine self-administration sessions without d-amphetamine. They then received 14 more sessions now either with (COC/COC + A rats) or without (COC/COC rats) concomitant d-amphetamine treatment. In both experiments, d-amphetamine-treated rats showed reduced motivation to take and seek cocaine, responding less for cocaine both under progressive ratio and extinction conditions. In contrast, d-amphetamine treatment did not influence cocaine-primed reinstatement of cocaine seeking. Thus, d-amphetamine treatment reduces both the development and expression of addiction-relevant patterns of cocaine use in female animals.

scholarly journals Intermittent self-administration of fentanyl induces a multifaceted addiction state associated with persistent changes in the orexin system

2020 ◽  
Author(s):  
Jennifer E. Fragale ◽  
Morgan H. James ◽  
Gary Aston-Jones
Keyword(s):  
Behavioral Economics ◽  
Receptor Antagonist ◽  
Critical Role ◽  
Opioid Addiction ◽  
Male Rats ◽  
Self Administration ◽  
Drug Seeking ◽  
Intermittent Access ◽  
Long Access

AbstractThe orexin (hypocretin) system plays a critical role in motivated drug-taking. Cocaine self-administration with the intermittent access (IntA) procedure produces a robust addiction-like state that is orexin-dependent. Here, we sought to determine the role of the orexin system in opioid addiction using IntA self-administration of fentanyl. Different groups of male rats were either given continuous access in 1h (short access; ShA), or 6h periods (long access, LgA), or IntA (5min of access separated by 25min of no-access) to fentanyl for 14 days. IntA produced a greater escalation of fentanyl intake, motivation for fentanyl on a behavioral economics task, persistent drug seeking during abstinence, and cued-induced reinstatement compared to rats given ShA or LgA. We found that addiction behaviors induced by IntA to fentanyl were reversed by the orexin-1 receptor antagonist SB-334867. IntA to fentanyl was also associated with a persistent increase in the number of orexin-expressing neurons. Together, results indicate that the IntA model is a useful tool in the study of opioid addiction, and that the orexin system is critical for the maintenance of addiction behaviors induced by IntA self-administration of fentanyl.

scholarly journals Sex differences in cocaine self-administration behaviour under Long Access versus Intermittent Access conditions

2018 ◽  
Author(s):  
Hajer Algallal ◽  
Florence Allain ◽  
Ndeye Aissatou Ndiaye ◽  
Anne-Noel Samaha
Keyword(s):  
Sex Differences ◽  
Progressive Ratio ◽  
Incentive Motivation ◽  
Cocaine Addiction ◽  
Male Rats ◽  
Locomotor Sensitization ◽  
Self Administration ◽  
Cocaine Use ◽  
Intermittent Access ◽  
Long Access

A widely accepted rodent model to study cocaine addiction involves allowing animals continuous access to drug during long self-administration sessions (Long-access or LgA). This produces continuously high brain concentrations of drug during each session. This might not model the pharmacokinetics of cocaine use in experienced human users, which are thought to involve intermittently spiking brain cocaine concentrations within and between bouts of use. Intermittent-access (IntA) cocaine self-administration models this spiking pattern in rats. IntA is also particularly effective in increasing incentive motivation for drug. Most IntA studies have been conducted in male rats. Both humans and non-human animals can show sex differences in all phases of the addiction process. We compared cocaine use in female and male rats that self-administered the drug (0.25 mg/kg/injection, i.v.) during 10 daily, 6-h LgA or IntA sessions. Cocaine intake was greatest under LgA, and female LgA rats escalated their intake. However, only IntA rats (both sexes) developed locomotor sensitization to self-administered cocaine and sensitization was greatest in the females. Five and 25 days after the last self-administration session, we quantified incentive motivation for cocaine by measuring breakpoints for the drug (0.083-0.75 mg/kg/injection) under progressive ratio. Breakpoints were similar in IntA and LgA rats. There were no sex differences in breakpoints under LgA. However, under IntA, females reached higher breakpoints for cocaine than males. Thus, LgA might be best suited to study sex differences in cocaine intake, while IntA might be best suited to study sex differences in incentive motivational processes in cocaine addiction.

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.

scholarly journals Fostering itself increases nicotine self-administration in young adult male rats

2013 ◽  
Vol 229 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Emily E. Roguski ◽  
Hao Chen ◽  
Burt M. Sharp ◽  
Shannon G. Matta
Keyword(s):  
Young Adult ◽  
Adult Male ◽  
Male Rats ◽  
Self Administration ◽  
Young Adult Male

Treadmill exercise reduces self-administration of morphine in male rats

2009 ◽  
Vol 16 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Mahmoud Hosseini ◽  
Hojjat Allah Alaei ◽  
Asieh Naderi ◽  
Mohammad Reza Sharifi ◽  
Reza Zahed
Keyword(s):  
Treadmill Exercise ◽  
Male Rats ◽  
Self Administration

Role of neuropeptide neuromedin U in the nucleus accumbens shell in cocaine self-administration in male rats

2021 ◽  
Author(s):  
James M. Kasper ◽  
Ashley E. Smith ◽  
Sierra N. Miller ◽  
Ara ◽  
William K. Russell ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Male Rats ◽  
Nucleus Accumbens Shell ◽  
Self Administration

scholarly journals Disruption of VGLUT1 in cholinergic medial habenula projections increases nicotine self-administration

2021 ◽  
Author(s):  
Elizabeth A Souter ◽  
Yen-Chu Chen ◽  
Vivien Zell ◽  
Valeria Lallai ◽  
Thomas Steinkellner ◽  
...  
Keyword(s):  
Cholinergic Neurons ◽  
Nicotine Addiction ◽  
Conditional Knockout ◽  
Self Administration ◽  
Interpeduncular Nucleus ◽  
Medial Habenula ◽  
Field Assay ◽  
Nicotine Consumption ◽  
Additional Support ◽  
Cholinergic Projections

Cholinergic projections from the medial habenula (MHb) to the interpeduncular nucleus (IPN) have been studied for their complex contributions to nicotine addiction and have been implicated in nicotine reinforcement, aversion, and withdrawal. While it has been established that MHb cholinergic projections co-release glutamate, no direct evidence has demonstrated a role for this specific glutamate projection in nicotine consumption. In the present study, a novel floxed Slc17a7 (VGLUT1) mouse was generated and used to create conditional knockout (cKO) mice that lack VGLUT1 in MHb cholinergic neurons. Histochemical approaches and optogenetics-assisted electrophysiology were used to validate the disruption of VGLUT1 from cholinergic MHb to IPN projections. The mice displayed no gross phenotypic abnormalities and exhibited normal exploratory and locomotor behavior in the open-field assay. However, the loss of VGLUT1-mediated glutamate co-release led to increased nicotine self-administration. These findings indicate that glutamate co-release from ventral MHb cholinergic neurons opposes nicotine consumption and provide additional support for targeting this synapse to develop potential treatments to nicotine addiction.

Sign in / Sign up

Export Citation Format

Share Document