scholarly journals SHORTENING TIME FOR ALCOHOL ACCESS DRIVES UP FRONT-LOADING BEHAVIOR, BRINGING CONSUMPTION IN MALE RATS TO THE LEVEL OF FEMALES

2021 ◽  
Author(s):  
Annabelle Flores-Bonilla ◽  
Barbara De Oliveira ◽  
Andrea Silva-Gotay ◽  
Kyle W. Lucier ◽  
Heather N. Richardson
Keyword(s):  
Sex Differences ◽  
Alcohol Drinking ◽  
Drinking Behavior ◽  
Fixed Ratio ◽  
Male Rats ◽  
Drinking Patterns ◽  
Self Administration ◽  
Dark Cycle ◽  
Female Wistar Rats ◽  
Total Alcohol

Alcohol can have more detrimental effects on mental health in women, even when intake is comparable or higher in men. This may relate to a differential pattern of drinking, e.g., how rapidly alcohol is consumed. We used operant procedures to gain insight into sex differences in the drinking dynamics of rats. Adult male and female Wistar rats underwent operant training to promote voluntary drinking of 10% (w/v) alcohol (8 rats/sex). We tested how drinking patterns changed after manipulating the effort required for alcohol (fixed ratio, FR), as well as the length of time in which animals had access to alcohol (self-administration session length). Rats were tested twice within the 12 hours of the dark cycle, at 2 hours (early sessions) and 10 hours into the dark cycle (late sessions). As expected, adult females consumed significantly more alcohol than males in the 30-minute sessions with the FR1 paradigm. Alcohol consumption within females was higher in the late sessions compared to early sessions, whereas this difference was not found within males. Front-loading of alcohol (heavier drinking in the first five minutes of the session) was the primary factor underlying higher consumption in females, and this sex difference was accentuated in the late sessions. Increasing the effort required from FR1 to FR3 reduced alcohol drinking in both sexes. Front-loading behavior remained in females in both early and late sessions, whereas males exhibited minimal front-loading behavior only in the early sessions. Compressing drinking access to 15-minutes drove up front-loading behavior, producing total alcohol intake levels that were comparable in both sexes. This strategy could be useful for exploring sex differences in the effect of voluntary alcohol drinking on the brain. Our findings also highlight the importance of the time of testing for detecting sex differences in drinking behavior.

scholarly journals Shortening time for access to alcohol drives up front-loading behavior, bringing consumption in male rats to the level of females

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Annabelle Flores-Bonilla ◽  
Barbara De Oliveira ◽  
Andrea Silva-Gotay ◽  
Kyle W. Lucier ◽  
Heather N. Richardson
Keyword(s):  
Sex Differences ◽  
Alcohol Drinking ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Drinking Patterns ◽  
Self Administration ◽  
Dark Cycle ◽  
Male And Female ◽  
Schedule Of Reinforcement

Abstract Background Incentives to promote drinking (“happy hour”) can encourage faster rates of alcohol consumption, especially in women. Sex differences in drinking dynamics may underlie differential health vulnerabilities relating to alcohol in women versus men. Herein, we used operant procedures to model the happy hour effect and gain insight into the alcohol drinking dynamics of male and female rats. Methods Adult male and female Wistar rats underwent operant training to promote voluntary drinking of 10% (w/v) alcohol (8 rats/sex). We tested how drinking patterns changed after manipulating the effort required for alcohol (fixed ratio, FR), as well as the length of time in which rats had access to alcohol (self-administration session length). Rats were tested twice within the 12 h of the dark cycle, first at 2 h (early phase of the dark cycle, “early sessions”) and then again at 10 h into the dark cycle (late phase of the dark cycle, “late sessions”) with an 8-h break between the two sessions in the home cage. Results Adult females consumed significantly more alcohol (g/kg) than males in the 30-min sessions with the FR1 schedule of reinforcement when tested late in the dark cycle. Front-loading of alcohol was the primary factor driving higher consumption in females. Changing the schedule of reinforcement from FR1 to FR3 reduced total consumption. Notably, this manipulation had minimal effect on front-loading behavior in females, whereas front-loading behavior was significantly reduced in males when more effort was required to access alcohol. Compressing drinking access to 15 min to model a happy hour drove up front-loading behavior, generating alcohol drinking patterns in males that were similar to patterns in females (faster drinking and higher intake). Conclusions This strategy could be useful for exploring sex differences in the neural mechanisms underlying alcohol drinking and related health vulnerabilities. Our findings also highlight the importance of the time of testing for detecting sex differences in drinking behavior.

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 Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to Intoxication

2021 ◽  
Vol 11 (2) ◽  
pp. 189
Author(s):  
Bryan E. Jensen ◽  
Kayla G. Townsley ◽  
Kolter B. Grigsby ◽  
Pamela Metten ◽  
Meher Chand ◽  
...  
Keyword(s):  
Drinking Behavior ◽  
Effective Means ◽  
Fixed Ratio ◽  
Progressive Ratio ◽  
Blood Alcohol ◽  
Drinking Patterns ◽  
Self Administration ◽  
Blood Alcohol Levels ◽  
Drinking In The Dark ◽  
Mouse Lines

Alcohol use disorder (AUD) is a devastating psychiatric disorder that has significant wide-reaching effects on individuals and society. Selectively bred mouse lines are an effective means of exploring the genetic and neuronal mechanisms underlying AUD and such studies are translationally important for identifying treatment options. Here, we report on behavioral characterization of two replicate lines of mice that drink to intoxication, the High Drinking in the Dark (HDID)-1 and -2 mice, which have been selectively bred (20+ generations) for the primary phenotype of reaching high blood alcohol levels (BALs) during the drinking in the dark (DID) task, a binge-like drinking assay. Along with their genetically heterogenous progenitor line, Hs/Npt, we tested these mice on: DID and drinking in the light (DIL); temporal drinking patterns; ethanol sensitivity, through loss of righting reflex (LORR); and operant self-administration, including fixed ratio (FR1), fixed ratio 3:1 (FR3), extinction/reinstatement, and progressive ratio (PR). All mice consumed more ethanol during the dark than the light and both HDID lines consumed more ethanol than Hs/Npt during DIL and DID. In the dark, we found that the HDID lines achieved high blood alcohol levels early into a drinking session, suggesting that they exhibit front loading like drinking behavior in the absence of the chronicity usually required for such behavior. Surprisingly, HDID-1 (female and male) and HDID-2 (male) mice were more sensitive to the intoxicating effects of ethanol during the dark (as determined by LORR), while Hs/Npt (female and male) and HDID-2 (female) mice appeared less sensitive. We observed lower HDID-1 ethanol intake compared to either HDID-2 or Hs/Npt during operant ethanol self-administration. There were no genotype differences for either progressive ratio responding, or cue-induced ethanol reinstatement, though the latter is complicated by a lack of extinguished responding behavior. Taken together, these findings suggest that genes affecting one AUD-related behavior do not necessarily affect other AUD-related behaviors. Moreover, these findings highlight that alcohol-related behaviors can also differ between lines selectively bred for the same phenotype, and even between sexes within those same line.

scholarly journals Sex Differences in the Effect of Alcohol Drinking on Myelinated Axons in the Anterior Cingulate Cortex of Adolescent Rats

2019 ◽  
Vol 9 (7) ◽  
pp. 167
Author(s):  
Tavares ◽  
Silva-Gotay ◽  
Riad ◽  
Bengston ◽  
Richardson
Keyword(s):  
Sex Differences ◽  
Alcohol Drinking ◽  
Alcohol Exposure ◽  
Anterior Cingulate ◽  
Myelinated Fiber ◽  
Drinking Patterns ◽  
Self Administration ◽  
Fiber Density ◽  
Myelinated Axons ◽  
Nodal Domains

Cognitive deficits associated with teenage drinking may be due to disrupted myelination of prefrontal circuits. To better understand how alcohol affects myelination, male and female Wistar rats (n = 7–9/sex/treatment) underwent two weeks of intermittent operant self-administration of sweetened alcohol or sweetened water early in adolescence (postnatal days 28–42) and we tested for macro- and microstructural changes to myelin. We previously reported data from the males of this study showing that alcohol drinking reduced myelinated fiber density in layers II–V of the anterior cingulate division of the medial prefrontal cortex (Cg1); herein, we show that myelinated fiber density was not significantly altered by alcohol in females. Alcohol drinking patterns were similar in both sexes, but males were in a pre-pubertal state for a larger proportion of the alcohol exposure period, which may have contributed to the differential effects on myelinated fiber density. To gain more insight into how alcohol impacts myelinated axons, brain sections from a subset of these animals (n = 6/sex/treatment) were used for microstructural analyses of the nodes of Ranvier. Confocal analysis of nodal domains, flanked by immunofluorescent-labeled contactin-associated protein (Caspr) clusters, indicated that alcohol drinking reduced nodal length-to-width ratios in layers II/III of the Cg1 in both sexes. Despite sex differences in the underlying cause (larger diameter axons after alcohol in males vs. shorter nodal lengths after alcohol in females), reduced nodal ratios could have important implications for the speed and integrity of neural transmission along these axons in both males and females. Alcohol-induced changes to myelinated axonal populations in the Cg1 may contribute to long-lasting changes in prefrontal function associated with early onset drinking.

scholarly journals Differential Effects of Saikosaponins A, B2, B4, C and D on Alcohol and Chocolate Self-Administration in Rats

2020 ◽  
Vol 55 (4) ◽  
pp. 367-373
Author(s):  
Paola Maccioni ◽  
Irene Lorrai ◽  
Federica Fara ◽  
Mauro A M Carai ◽  
Gian Luigi Gessa ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Fixed Ratio ◽  
Male Rats ◽  
Schedules Of Reinforcement ◽  
Self Administration ◽  
Structural Differences ◽  
Addictive Potential ◽  
Bupleurum Falcatum ◽  
Saikosaponin A

Abstract Aims Treatment with saikosaponin A (SSA)—an ingredient of the medicinal herb, Bupleurum falcatum—has been reported to suppress several addictive-like behaviors, including morphine, cocaine, alcohol and chocolate self-administration in male rats. The aim of this investigation was to investigate whether saikosaponins of B. falcatum other than SSA affect alcohol and chocolate self-administration in rats. Methods Ovariectomized female Sardinian alcohol-preferring (sP) and Wistar rats were trained to self-administer alcohol (15%, v/v) and a chocolate solution [5% (w/v) Nesquik® in water], respectively, under fixed ratio schedules of reinforcement. The following saikosaponins were compared to SSA: saikosaponin D (SSD; epimer of SSA), saikosaponin C (SSC), saikosaponin B2 (SSB2) and saikosaponin B4 (SSB4). All saikosaponins were tested acutely at the doses of 0, 0.25, 0.5 and 1 mg/kg (i.p.). Results Treatment with SSA and SSD resulted in highly similar, marked reductions in alcohol self-administration; SSC failed to alter lever-responding for alcohol, while SSB2 and SSB4 produced intermediate reductions. Only SSA and SSD reduced chocolate self-administration, with SSC, SSB2 and SSB4 being ineffective. Conclusions The wide spectrum of efficacy of saikosaponins in reducing alcohol and chocolate self-administration suggests that even relatively small structural differences are sufficient to produce remarkable changes in their in vivo pharmacological profile. Together, these results confirm that roots of B. falcatum may be an interesting source of compounds with anti-addictive potential.

scholarly journals 2276

2017 ◽  
Vol 1 (S1) ◽  
pp. 33-34
Author(s):  
Alyssa Schneider ◽  
Bethany L. Stangl ◽  
Elgin R. Yalin ◽  
Jodi M. Gilman ◽  
Vijay Ramchandani
Keyword(s):  
Alcohol Use ◽  
Social Influence ◽  
Drinking Behavior ◽  
Impulsive Behavior ◽  
Drinking Patterns ◽  
Self Administration ◽  
Neo Personality Inventory ◽  
Priming Phase ◽  
Delayed Discounting ◽  
The Relationship

OBJECTIVES/SPECIFIC AIMS: Impulsivity is a significant predictor of alcohol use and drinking behavior, and has been shown to be a critical trait in those with alcohol use disorder. Suggestibility, or susceptibility to social influence, has been shown to correlate with impulsivity, with highly suggestible individuals being more likely to make impulsive decisions influenced by peer groups. However, the relationship between social influence and drinking behavior is unclear. Our objective was to describe the relationship between social influence and impulsivity traits using the social delayed discounting task and potential differences in intravenous alcohol self-administration (IV-ASA) behavior. METHODS/STUDY POPULATION: Healthy, non-dependent drinkers (n=20) completed a CAIS session, which consisted of an initial 25-minute priming phase, where subjects were prompted to push a button to receive individually standardized IV alcohol infusions, followed by a 125-minute phase during which they could push the button for additional infusions. IV-ASA measures included the peak (PEAK) and average (AVG) BrAC and Number of Button Presses (NBP). Participants completed a social delayed discounting task (SDDT), where participants were presented with the choice of a small, sooner (SS) reward or a large, later (LL) reward. Before starting the task, participants chose peers who selected either the impulsive (SI) or non-impulsive choice (S). Intermittently, the peers’ choice was not shown (X) or different choices (D) were selected. Participants also completed the MISS, the Barratt Impulsiveness Scale (BIS-11), UPPS-P Impulsive Behavior Scale, and the NEO personality inventory. RESULTS/ANTICIPATED RESULTS: Participants with higher suggestibility scores had greater NBP, AVG, and PEAK BrAC in the early phase of the IV-ASA session. Higher scores on the MISS were also correlated with higher impulsivity scores including the NEO Neuroticism (N-factor) measure, BIS-11, and UPPS-P. Results also showed that the MISS score was inversely correlated with the percent of impulsive choices in the SDDT, but that this was independent of peers’ impulsive or nonimpulsive choices. DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate that non-dependent drinkers that were more susceptible to social influence had heavier drinking patterns, higher IV-ASA, and higher scores on impulsivity measures. In addition, individuals that were more susceptible to social influence made more impulsive choices in general, but those choices were not affected by peer decisions during the task. As such, susceptibility to social influence may be an important determinant of impulsive choices, particularly in relation to alcohol consumption.

5-HT1B receptor agonist attenuates cocaine self-administration after protracted abstinence and relapse in rats

2021 ◽  
pp. 026988112110192
Author(s):  
Samantha N Scott ◽  
Raul Garcia ◽  
Gregory L Powell ◽  
Sophia M Doyle ◽  
Brielle Ruscitti ◽  
...  
Keyword(s):  
Cue Reactivity ◽  
Fixed Ratio ◽  
Test Session ◽  
Female Rats ◽  
Male Rats ◽  
Inhibitory Effects ◽  
Self Administration ◽  
Training Dose ◽  
Male And Female Rats ◽  
Cocaine Seeking

Background: The 5-HT1B receptor (5-HT1BR) agonist, CP94253, enhances cocaine intake during maintenance of self-administration (SA) but attenuates intake after 21 days of forced abstinence in male rats. Aims: We examined whether CP94253 attenuates cocaine intake in female rats after a period of abstinence, and if these attenuating effects persist or revert to enhancing cocaine intake during resumption (i.e. relapse) of daily cocaine SA. Methods: Male and female rats trained to lever press on a fixed ratio 5 schedule of cocaine reinforcement underwent ⩾21 days of forced abstinence. They were then tested for the effects of CP94253 (5.6 mg/kg, SC) or vehicle on cocaine SA. During the test session, rats had 1-h access to the training dose of cocaine (0.75 mg/kg, IV) followed by 1-h access to a lower cocaine dose (0.075 mg/kg, IV). Rats then resumed cocaine SA for 15 days to mimic relapse and were retested as done previously. Subsequently, rats underwent abstinence again (21–60 days) and were tested for CP94253 effects on locomotion and cue reactivity (i.e. responding for light/tone cues previously paired with cocaine infusions). Results: Regardless of sex, CP94253 decreased cocaine intake after abstinence and during resumption of SA and decreased cue reactivity while having no effect on locomotion. Conclusions: CP94253 decreases cocaine intake and cocaine seeking in both males and females even after resumption of cocaine SA. These findings suggest that the inhibitory effects of CP94253 observed after abstinence are long-lasting, and therefore, 5-HT1BR agonists may have clinical efficacy as anti-relapse medications for cocaine use disorders.

scholarly journals Δ9-tetrahydrocannabinol Attenuates Oxycodone Self-Administration Under Extended Access Conditions

2017 ◽  
Author(s):  
Jacques D. Nguyen ◽  
Yanabel Grant ◽  
Kevin M. Creehan ◽  
Candy S. Hwang ◽  
Sophia A. Vandewater ◽  
...  
Keyword(s):  
Male Rats ◽  
Medical Cannabis ◽  
Self Administration ◽  
Extended Access ◽  
Antinociceptive Effects ◽  
Nonmedical Use ◽  
Vehicle Treatment ◽  
Female Wistar Rats ◽  
Dose Dependent

AbstractGrowing nonmedical use of prescription opioids is a global problem, motivating research on ways to reduce use and combat addiction. Medical cannabis (“medical marijuana”) legalization has been associated epidemiologically with reduced opioid harms and cannabinoids have been shown to modulate effects of opioids in animal models. This study was conducted to determine if Δ9-tetrahydrocannabinol (THC) enhances the behavioral effects of oxycodone.Male rats were trained to intravenously self-administer (IVSA) oxycodone (0.15 mg/kg/infusion) during 1 h, 4 h or 8 h sessions. Following acquisition rats were exposed to THC by vapor inhalation (1 h and 8 h groups) or injection (0-10 mg/kg, i.p.; all groups) prior to IVSA sessions. Fewer oxycodone infusions were obtained by rats following vaporized or injected THC compared with vehicle treatment prior to the session. Follow-up studies demonstrated parallel dose-dependent effects of THC, i.p., on self-administration of different per-infusion doses of oxycodone and a preserved loading dose early in the session. These patterns are inconsistent with behavioral suppression. Additional groups of male and female Wistar rats were assessed for nociception following inhalation of vaporized THC (50 mg/mL), oxycodone (100 mg/mL) or the combination. Tail withdrawal latency was increased more by the THC/oxycodone combination compared to either drug alone. Similar additive antinociceptive effects were produced by injection of THC (5.0 mg/kg, i.p.) and oxycodone (2.0 mg/kg, s.c.). Together these data demonstrate additive effects of THC and oxycodone and suggest the potential use of THC to enhance therapeutic efficacy, and to reduce the abuse, of opioids.

scholarly journals Locomotor and Reinforcing Effects of Pentedrone, Pentylone and Methylone in Rats

2017 ◽  
Author(s):  
Mehrak Javadi-Paydar ◽  
Jacques D. Nguyen ◽  
Sophia A. Vandewater ◽  
Tobin J. Dickerson ◽  
Michael A. Taffe
Keyword(s):  
Wistar Rats ◽  
Second Generation ◽  
Female Rats ◽  
Dose Effect ◽  
Male Rats ◽  
Structural Motif ◽  
Self Administration ◽  
Male And Female ◽  
Female Wistar Rats ◽  
Reinforcing Effects

AbstractThe broad diversity of synthetic cathinone psychostimulant drugs that are available to users complicates research efforts to provide understanding of health risks. Second generation cathinones pentedrone and pentylone are distinguished from each other by the 3,4-methylenedioxy structural motif (which distinguishes methamphetamine from 3,4-methylenedioxymethamphetamine) and each incorporates the α-alkyl chain motif contained in the transporter-inhibitor cathinones (3,4-methylenedioxypyrovalerone (MDPV), α-pyrrolidinopentiophenone (α-PVP)) but not in the monoamine releasers (mephedrone, methylone). Studies were conducted in male and female Wistar rats to compare locomotor and thermoregulatory effects of pentedrone, pentylone and methylone using an implanted radiotelemetry system. Reinforcing effects were assessed in female Wistar rats trained in the intravenous self-administration (IVSA) procedure and subjected to dose-substitution (0.025-0.3 m/gkg/inf) under a fixed-ratio 1 response contingency. Pentedrone, pentylone and methylone dose-effect curves were contrasted with those for α-PVP and α-pyrrolidinohexiophenone (α-PHP). Dose dependent increases in locomotion were observed after intraperitoneal injection of pentylone (0.5-10.0 mg/kg), pentedrone (0.5-10.0 mg/kg) or mephedrone (0.5-10.0 mg/kg) in male and female rats. The maximum locomotor effect was similar across drugs but lasted longest after pentedrone. Mean body temperature did not vary systematically more than 0.5 °C after pentedrone or pentylone in either sex. A sustained hyperthermia (0.4-0.8 °C) was observed for four hours after 10 mg/kg methylone in male rats. More infusions of pentedrone or pentylone were self-administered compared with methylone, but all three were less potent than α-PVP or α-PHP. These studies support the inference that second generation cathinones pentylone and pentedrone have abuse liability greater than that of methylone.

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