Effects of noncontingent ethanol, DHEA, and pregnanolone administration on ethanol self-administration in outbred female rats. 2019

Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States. Electronic address: lerwin@lsuhsc.edu.

Previous research from this laboratory demonstrated that male outbred rats (Long-Evans) can be trained to prefer ethanol (10% v/v) over water during 30-min home-cage sessions and that higher ethanol concentrations (18-32% v/v) can serve as a reinforcer under various operant schedules. Further, we have shown that two neurosteroids, dehydroepiandrosterone (DHEA) and pregnanolone, can readily decrease ethanol self-administration in males. The present study used the same procedures in an attempt to systematically replicate the previous findings in female outbred rats. Rats were first trained to self-administer ethanol in the home cage using a saccharin-fading procedure. Subsequently, a two-bottle preference test was initiated by substituting different ethanol concentrations after subjects reliably consumed 10% ethanol alone. Water was always available during this phase. Next, subjects were transitioned to a fixed-ratio 10 (FR-10) schedule of reinforcement with 0.1 mL of ethanol (18% v/v) serving as the reinforcer so that a concentration-effect curve could be established. Upon completion, subjects were transitioned to an FR-10 FR-20 multiple schedule of ethanol (32% v/v) and food reinforcement to determine whether noncontingent ethanol, DHEA, and pregnanolone could selectively decrease ethanol intake. Not surprisingly, female subjects preferentially consumed ethanol over water at concentrations of 3.2-18% (v/v) during the home-cage procedure, and significantly increased the mean dose of ethanol consumed and blood ethanol concentration (BEC). Similarly, increasing concentrations under an FR-10 schedule significantly increased the dose of ethanol presented and BEC compared to control (water). Finally, under the multiple schedule, noncontingent injections of ethanol (0.32-1.8 g/kg), DHEA (10-100 mg/kg), and pregnanolone (1.8-32 mg/kg) dose-dependently decreased food- and ethanol-maintained responding and the dose of ethanol presented. BEC was significantly decreased by the neurosteroids, but increased by ethanol due to its noncontingent administration. Together, these data replicate only a subset of the data previously obtained in males, suggesting there are sex differences particularly with respect to the effects of DHEA and pregnanolone.

UI MeSH Term Description Entries
D011280 Pregnanolone A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties. Eltanolone,3 alpha, 5 beta-Tetrahydroprogesterone,3 alpha-Hydroxy-5 alpha-pregnan-20-one,3 alpha-Hydroxy-5 beta-pregnan-20-one,3-Hydroxypregnan-20-one,3beta-Hydroxy-5alpha-pregnan-20-one,Allopregnan-3 beta-ol-20-one,Allopregnanolone,Epipregnanolone,Pregnan-3alpha-ol-20-one,Pregnanolone, (3alpha)-isomer,Pregnanolone, (3alpha, 5beta, 17-alpha)-isomer,Pregnanolone, (3alpha,5alpha)-isomer,Pregnanolone, (3alpha,5beta)-isomer,Pregnanolone, (3beta)-isomer,Pregnanolone, (3beta, 5alpha)-isomer,Pregnanolone, (3beta, 5alpha, 17alpha)-isomer,Pregnanolone, (3beta, 5alpha, 8alpha, 17beta)-isomer,Pregnanolone, (3beta, 5beta)-isomer,Pregnanolone, (3beta, 5beta, 17alpha)-isomer,Pregnanolone, (3beta, 5beta,14beta)-isomer,Pregnanolone, (5alpha)-isomer,Sepranolone,3 Hydroxypregnan 20 one,3 alpha Hydroxy 5 alpha pregnan 20 one,3 alpha Hydroxy 5 beta pregnan 20 one,3 alpha, 5 beta Tetrahydroprogesterone,3beta Hydroxy 5alpha pregnan 20 one,Allopregnan 3 beta ol 20 one,Pregnan 3alpha ol 20 one,alpha-Hydroxy-5 alpha-pregnan-20-one, 3,alpha-Hydroxy-5 beta-pregnan-20-one, 3,alpha-pregnan-20-one, 3 alpha-Hydroxy-5,beta-ol-20-one, Allopregnan-3,beta-pregnan-20-one, 3 alpha-Hydroxy-5
D012055 Reinforcement Schedule A schedule prescribing when the subject is to be reinforced or rewarded in terms of temporal interval in psychological experiments. The schedule may be continuous or intermittent. Reinforcement Schedules,Schedule, Reinforcement,Schedules, Reinforcement
D003687 Dehydroepiandrosterone A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion. Dehydroisoandrosterone,Prasterone,5-Androsten-3-beta-hydroxy-17-one,5-Androsten-3-ol-17-one,Androstenolone,DHEA,Prasterone, 3 alpha-Isomer,5 Androsten 3 beta hydroxy 17 one,5 Androsten 3 ol 17 one,Prasterone, 3 alpha Isomer
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D000428 Alcohol Drinking Behaviors associated with the ingesting of ALCOHOLIC BEVERAGES, including social drinking. Alcohol Consumption,Alcohol Intake,Drinking, Alcohol,Alcohol Drinking Habits,Alcohol Drinking Habit,Alcohol Intakes,Consumption, Alcohol,Drinking Habit, Alcohol,Habit, Alcohol Drinking,Habits, Alcohol Drinking,Intake, Alcohol
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012646 Self Administration Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. Administration, Self,Administrations, Self,Self Administrations
D016896 Treatment Outcome Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series. Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes

Related Publications

Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
July 2009, Pharmacology, biochemistry, and behavior,
Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
July 2009, Alcoholism, clinical and experimental research,
Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
March 2015, Alcohol (Fayetteville, N.Y.),
Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
October 2014, Behavioural pharmacology,
Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
November 1996, Psychopharmacology,
Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
January 2004, Alcohol and alcoholism (Oxford, Oxfordshire),
Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
September 2020, Alcohol (Fayetteville, N.Y.),
Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
December 2001, Behavioral neuroscience,
Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
January 1994, Alcohol (Fayetteville, N.Y.),
Laura L Erwin, and Mark R Nilges, and Alyssa F DeLarge, and Peter F Weed, and Peter J Winsauer
November 2000, Pharmacology, biochemistry, and behavior,
Copied contents to your clipboard!