Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 5T32AA007222-09 from National Institute On Alcohol Abuse And Alcoholism IRG: ALCP
Project start date: 1978-07-01
Project end date: 1987-06-30
Sponsored Links Excellgen http://Excellgen.com
BIOPSYCHOLOGY TRAINING IN ALCOHOL RESEARCH
Frank A Holloway, Professor
Psychiatry And Behavioral Scisuniversity Of Oklahoma Hlth Sciences Ctr
health Sciences Center
oklahoma City, Ok 731171213
Grant 5T32AA007222-23 from National Institute On Alcohol Abuse And Alcoholism IRG: ZAA1
Abstract: Purpose and Program Characteristics The purpose of the proposed program is to provide research training for 5 predoctoral (Ph.D.), 3 postdoctoral trainees, and 4 medical students (summer) in biobehavioral approaches to the study of alcohol abuse and alcoholism, with the specific objective of producing competent, independent investigators. Through specific courses, seminars, clinical research practice, and laboratory research, these trainees will (1) acquire research methodologies relevant to alcohol abuse alcoholism areas; (2) develop an appreciation of the biomedical, biobehavioral and clinical aspects of alcoholism and the acute and chronic effects of alcohol; and (3) apply the latter knowledge base and skills in designing and executing original research in this area. We have identified several research areas for which faculty supervision and research facilities are available behavioral pharmacology, behavioral genetics, electrophysiology/neurophysiology (both human and animal studies), human performance and neuropsychology, psychophysiology (both human and animal studies), and neurochemistry. Current research opportunities include the following tolerance and other drug history factors in alcohol reward effects, antiintoxicants and alcohol self-administration, metabolic and oxidative stress factors in acute and chronic alcohol effects, electrophysiological and behavioral characteristics of alcohol withdrawal, the interaction of alcohol, exercise, and family history on cardiovascular reactivity, residual effects of chronic alcohol exposure on human cognitive processes and electrophysiology acute and chronic alcohol effects on auditory/vestibular neural systems and on brain neurochemistry, gender differences in human subjective effects of alcohol, acute alcohol and hangover effects on human performance and mood, and genetic (inbred strain) analyses of behavioral/neurochemical responsiveness to drugs of abuse. Trainees. Postdoctoral candidates will usually have a Ph.D. in clinical or experimental psychology or in some other biomedical specialty or have an M.D. with residency training psychiatry and will be selected on the basis of research potential. Individuals with an M.D. degree and minorities with doctoral degrees applicants will be encouraged to apply. Predoctoral trainees should have strong undergraduate training in psychology and other biological sciences or be candidates for the M.D./Ph.D. program in the College of Medicine. Special effort will be made to recruit minority candidates. Trainees who complete either program will be qualified for research related positions in a number of settings, including academic, medical center, or clinical research programs
Project start date: 1978-07-01
Project end date: 2002-06-30
5T32AA007222-23 (2000): $276340
5T32AA007222-22 (1999): $242875
5T32AA007222-21 (1998): $225053
5T32AA007222-19 (1996): $149314
5T32AA007222-17 (1994): $191699
5T32AA007222-16 (1993): $124246
BIOPSYCHOLOGY RESEARCH TRAINING IN ALCOHOLISM
Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 5T32AA007222-14 from National Institute On Alcohol Abuse And Alcoholism IRG: ALCB
Project start date: 1978-07-01
Project end date: 1992-06-30
Sponsored Links Excellgen http://Excellgen.com
Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 5T32AA007222-08 from National Institute On Alcohol Abuse And Alcoholism IRG: ALCP
Project start date: 1978-07-01
Project end date: 1987-06-30
Grants awarded to Frank A Holloway
ABUSE LIABILITY OF DRUG ADJUNCTS FOR COCAINE WITHDRAWL
Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 5R01DA004444-06 from National Institute On Drug Abuse IRG: DACB
Abstract: We have recently reported that "legal" over-the-counter stimulants, when combined in appropriate dose ratios could engender drug-appropriate responding in amphetamine and cocaine drug discrimination tasks in rats. These results suggest that these legal stimulants may mimic the subjective effects of these psychomotor stimulants. Little is known about the abuse liability profile of these duplicitous drugs. The present proposal would extend the analysis of these legal stimulant combinations (e.g., caffeine (CAF), ephedrine (EPH), and phenylpropanolamine (PPA)). Project I utilizes a 4-hour limited access cocaine self-administration task to assess the "reinforcing" properties of these duplicitous drug combinations using (1) substitution tests, (2) preloading, and (3) progressive ratio schedules of reinforcement. Food and water will be available 20 h per day under concurrent FR10 schedules of reinforcement. The total amount and pattern of food and water consumption will be used as an index of behavioral toxicity of all drug challenges/conditions. Project II is designed to assess the discriminative stimulus properties of dual and triple combinations of legal stimulants (CAF + EPH, CAF + PPA, and CAF + EPH + PPA) and the cross-generalization profiles with the prototypic psychomotor stimulants cocaine [COC], d-amphetamine, and methamphetamine. The influence of drug and experimental history on the self-administration of cocaine will be assessed in Project II also. Two groups of rats will be utilized to assess the relative contribution of drug discrimination history (COC vs. saline, and the CAF + EPH + PPA combination vs. saline) on subsequent self-administration of COC. Three other groups will be yoked to the subjects in these discrimination tasks to match for drug history. Project III will assess the affective components of the stimulant withdrawal syndrome using two different 3-choice drug discrimination tasks (5 mg/kg chlordiazepoxide vs. saline vs. 15 mg/kg pentylenetetrazol and .03 mg/kg haloperidol vs. saline vs. 10 mg/kg COC). High dose pretreatments and 3-day chronic periods of both COC and the triple stimulant combination will be used to assess the "rebound" phenomena. In sum, the biobehavioral assays in this proposal would provide information concerning the abuse liability profile of these "legal" stimulants relative to that for cocaine. If these duplicitous drug compounds mimic the subjective effects of cocaine but lack cocaine s robust rewarding property and its withdrawal and behaviorally toxic effects, they might eventually provide a potential "methadone-model" of cocaine supplementation therapy.
Project start date: 1987-05-01
Project end date: 1994-06-30
5R01DA004444-06 (1992): $138554
DRUG HISTORY FACTORS IN ETHANOL´S REINFORCING EFFECTS
Frank A Holloway, Professor
Psychiatry And Behavioral Scisuniversity Of Oklahoma Hlth Sciences Ctr
health Sciences Center
oklahoma City, Ok 731171213
Grant 5R01AA006351-06 from National Institute On Alcohol Abuse And Alcoholism IRG: ALCB
Abstract: Tolerance to ethanol (ETOH) develops when repeated exposure to a given dose results in a decreased effect for that dose and an increase in the dose required to reproduce the initial ETOH dose effect. While ETOH tolerance and dependence may develop independently, a possible relationship may exist between tolerance development and the acquisition of sustained ETOH intake and eventual physical dependence. For example, tolerance development or behavioral adjustments to the disruptive or dysphoric properties of ETOH might set the occasion for increased ETOH intake, by reducing the "costs" of drinking, thereby enhancing its reward effects. Prior studies using a pre/post ETOH administration design with schedule-controlled behaviors have demonstrated 2-3 fold shifts to the right in the dose-effect curves in the pre-session ETOH group, with only minor tolerance development in the post- session groups. However, recently post-session ETOH treatments have resulted in significant shifts in the dose-effect curves without any intoxicated practice sessions. These data suggested an acute ETOH delayed effect developing approximately 22 hours post-administration, produced rate reductions in operant performance. Tolerance to these delayed ETOH rate- reducing effects developed and affected the magnitude of ETOH tolerance to its acute intoxicating effects. Preliminary data from this laboratory, not only supports the hypothesis that development of behavioral tolerance may reverse ETOH´s aversive effects and "unmask" its underlying reward/hedonic properties, but also indicates drug/behavior histories involving ETOH oral self-administration (OSA) or ETOH discrimination may do the same. The present proposal represents a systematic examination of the role that development of behavioral tolerance may play in modulating ETOH´s motivational effects in a rat model. Project I of the present proposal will examine the development of tolerance to ETOH´s immediate and/or delayed effects using an FR-30 schedule of operant performance sensitive primarily to ETOH´s suppressant effects on behavior. Several controls will be used, including pre-session saline, post-session ETOH and groups with no ETOH or behavioral histories. We then will examine the contribution of such tolerance to ETOH´s subsequent motivational effects as measured by three different behavioral assays (a) conditioned place preference (or aversion), (b) conditioned taste aversion, and (c) oral ETOH acceptance and preference. Project II, using a pre-/post-chronic ETOH design, will systematically examine the impact that development of behavioral tolerance on several parameters of oral ethanol self-administration established by a "sucrose-fading" procedure, including (a) shifts in baseline ethanol concentration-consumption curve, (b) dose-effect analysis of ETOH´s immediate and delayed modulation of ETOH intake when given as a "bolus" prior to the OSA-session. The data generated by this research should clarify the role of (1) the relative contribution of ETOH´s acute and delayed behavioral effects on tolerance development; (2) the impact of such tolerance development on subsequent assays for ETOH´s positive-rewarding and/or negative-aversive properties; and (3) the impact of such tolerance development on ETOH consumption itself and on the manner in which such consumption is modulated by recent ETOH experience
Keywords: behavior modification, drug addiction, drug tolerance, ethanol, motivation, psychological reinforcement, toxicology alcoholic beverage consumption, avoidance behavior, biological model, blood test, data collection, dosage, drug administration rate /duration, operant conditioning, performance, reinforcer, self medication computer processing of laboratory data, gas chromatography, laboratory rat, microcomputer, statistics /biometry
Project start date: 1992-02-01
Project end date: 1996-01-31
5R01AA006351-06 (1994): $144942
5R01AA006351-05 (1993): $138766
DRUG HISTORY FACTORS IN ETHANOL S REINFORCING EFFECTS
Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 2R01AA006351-04A1 from National Institute On Alcohol Abuse And Alcoholism IRG: ALCB
Abstract: Tolerance to ethanol (ETOH) develops when repeated exposure to a given dose results in a decreased effect for that dose and an increase in the dose required to reproduce the initial ETOH dose effect. While ETOH tolerance and dependence may develop independently, a possible relationship may exist between tolerance development and the acquisition of sustained ETOH intake and eventual physical dependence. For example, tolerance development or behavioral adjustments to the disruptive or dysphoric properties of ETOH might set the occasion for increased ETOH intake, by reducing the "costs" of drinking, thereby enhancing its reward effects. Prior studies using a pre/post ETOH administration design with schedule-controlled behaviors have demonstrated 2-3 fold shifts to the right in the dose-effect curves in the pre-session ETOH group, with only minor tolerance development in the post- session groups. However, recently post-session ETOH treatments have resulted in significant shifts in the dose-effect curves without any intoxicated practice sessions. These data suggested an acute ETOH delayed effect developing approximately 22 hours post-administration, produced rate reductions in operant performance. Tolerance to these delayed ETOH rate- reducing effects developed and affected the magnitude of ETOH tolerance to its acute intoxicating effects. Preliminary data from this laboratory, not only supports the hypothesis that development of behavioral tolerance may reverse ETOH s aversive effects and "unmask" its underlying reward/hedonic properties, but also indicates drug/behavior histories involving ETOH oral self-administration (OSA) or ETOH discrimination may do the same. The present proposal represents a systematic examination of the role that development of behavioral tolerance may play in modulating ETOH s motivational effects in a rat model. Project I of the present proposal will examine the development of tolerance to ETOH s immediate and/or delayed effects using an FR-30 schedule of operant performance sensitive primarily to ETOH s suppressant effects on behavior. Several controls will be used, including pre-session saline, post-session ETOH and groups with no ETOH or behavioral histories. We then will examine the contribution of such tolerance to ETOH s subsequent motivational effects as measured by three different behavioral assays (a) conditioned place preference (or aversion), (b) conditioned taste aversion, and (c) oral ETOH acceptance and preference. Project II, using a pre-/post-chronic ETOH design, will systematically examine the impact that development of behavioral tolerance on several parameters of oral ethanol self-administration established by a "sucrose-fading" procedure, including (a) shifts in baseline ethanol concentration-consumption curve, (b) dose-effect analysis of ETOH s immediate and delayed modulation of ETOH intake when given as a "bolus" prior to the OSA-session. The data generated by this research should clarify the role of (1) the relative contribution of ETOH s acute and delayed behavioral effects on tolerance development; (2) the impact of such tolerance development on subsequent assays for ETOH s positive-rewarding and/or negative-aversive properties; and (3) the impact of such tolerance development on ETOH consumption itself and on the manner in which such consumption is modulated by recent ETOH experience.
Project start date: 1992-02-01
Project end date: 1996-01-31
2R01AA006351-04A1 (1992): $142567
BIOBEHAVIORAL CORRELATES OF ACUTE ETHANOL WITHDRAWAL
Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 5R01AA008338-03 from National Institute On Alcohol Abuse And Alcoholism IRG: ALCB
Abstract: The subjective experiences resulting from acute high doses of ethanol have been termed "hangover" in humans. The hangover effects, or the "ethanol delayed effects" (EDE) may reflect a subjective precursor of withdrawal illnesses demonstrated after chronic ethanol exposure and may be regarded as a miniature model of the ethanol withdrawal syndrome. The present proposal would extend the analysis of the EDE to three physiological measures across a longer time frame than previously reported and to both acute and chronic ethanol dosing regimens. Using a remote radio telemetry computer-based system, electroencephalographic activity, core body temperature, and gross motor activity will be monitored in 50 male Sprague-Dawley rats. High dose pretreatments of ethanol (1.0, 2.0, 3.0, and 4.0 g/kg) will be administered and recordings will be taken for 48 hours post-treatment. A one-week "wash out" period will be instituted between treatments. Two routes of administration (i.p. injections and ethanol inhalation) will be used for chronic ethanol dosing. The three physiological measures will be assessed during and for 120 hours after chronic treatments. Direct comparisons will be made between the EDE (rebound) and the chronic ethanol withdrawal syndrome in the same subjects. Multiple regression analysis and ANCOVA will attempt to dissociate whether the EDE and the ethanol withdrawal syndrome differ on a quantitative, qualitative, and/or temporal dimension. Assessment of the subjective effects of the acute ethanol exposure and resulting EDE (rebound) will be achieved by a two-choice drug discrimination task using pentylenetetrazol and saline in 12 male Sprague-Dawley rats. Test sessions will be conducted at various time points after 7 acute high dose pretreatments of ethanol. Two dependent measures (percentage of drug-appropriate responding, and rate of responding throughout the 10-minute experimental session) will be used. Two performance measures (schedule-controlled behavior) will also be used to measure the EDE in two groups of rats (n=12/group). Rats will be trained in either an FR-30 or DRL- 20 schedule operant task for food reinforcement. Once stable baseline performance is achieved, test sessions will be conducted at various time-points after acute high dose pretreatments of ethanol (from 15 minutes to 48 hours postinjection). The role of the acute physiological compensatory responses elicited by high doses of ethanol, their subjective and performance reduction effects, and their relationship to the chronic ethanol withdrawal syndrome may help to elucidate the functional role they may play in the development of tolerance and dependence.
Project start date: 1990-01-01
Project end date: 1993-12-31
5R01AA008338-03 (1992): $112570
5R01AA008338-08 (1999): $169494
5R01AA008338-07 (1998): $162975
5R01AA008338-06 (1997): $171306
BIOPSYCHOLOGY TRAINING IN DRUG ABUSE
Frank A Holloway, Professor
Psychiatry And Behavioral Scisuniversity Of Oklahoma Hlth Sciences Ctr
health Sciences Center
oklahoma City, Ok 731171213
Grant 5T32DA007248-05 from National Institute On Drug Abuse IRG: SRCD
Project start date: 1995-09-15
Project end date: 2003-06-30
5T32DA007248-05 (1999): $249946
5T32DA007248-04 (1998): $210724
Sponsored Links Excellgen http://Excellgen.com
5T32DA007248-03 (1997): $206144
BIOPSYCHOLOGY TRAINING IN ALCOHOL RESEARCH
Frank A Holloway, Professor
Psychiatry And Behavioral Scisuniversity Of Oklahoma Hlth Sciences Ctr
health Sciences Center
oklahoma City, Ok 731171213
Grant 2T32AA007222-20 from National Institute On Alcohol Abuse And Alcoholism IRG: ZAA1
Project start date: 1978-07-01
Project end date: 2002-06-30
2T32AA007222-20 (1997): $214223
BIOBEHAVIORAL CORRELATES OF ACUTE ETHANOL WITHDRAWAL
Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 5R01AA008338-05 from National Institute On Alcohol Abuse And Alcoholism IRG: ALCB
Project start date: 1990-01-01
Project end date: 1999-12-31
5R01AA008338-05 (1996): $166739
BIOPSYCHOLOGY TRAINING IN DRUG ABUSE
Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 5T32DA007248-02 from National Institute On Drug Abuse IRG: SRCD
Project start date: 1995-09-15
Project end date: 2000-07-31
5T32DA007248-02 (1996): $195268
BIOPSYCHOLOGY TRAINING IN ALCOHOL RESEARCH
Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 2T32AA007222-15 from National Institute On Alcohol Abuse And Alcoholism IRG: SRCA
Project start date: 1978-07-01
Project end date: 1997-06-30
2T32AA007222-15 (1992): $168479
BIOPSYCHOLOGY RESEARCH TRAINING IN ALCOHOLISM
Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 2T32AA007222-10 from National Institute On Alcohol Abuse And Alcoholism IRG: ALCB
Project start date: 1978-07-01
Project end date: 1992-06-30
Frank A Holloway, Professor
University Of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 731171213
Grant 2T32AA007222-05 from National Institute On Alcohol Abuse And Alcoholism IRG: ALCP
Project start date: 1978-07-01
Project end date: 1987-06-30