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COMPARISON OF DRUG EFFECTS ON RESPONDING PUNISHED BY PRESSURIZED AIR OR ELECTRIC-SHOCK DELIVERY IN SQUIRREL-MONKEYS - PENTOBARBITAL, CHLORDIAZEPOXIDE, D-AMPHETAMINE AND COCAINE

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 1979年第2期209卷 309-315页

作者： SPEALMAN, RD HARVARD UNIV SCH MED NEW ENGLAND REG PRIMATE RES CTR SOUTHBOROUGH MA 01772 USA HARVARD UNIV SCH MED DEPT PSYCHIAT PSYCHOBIOL LAB BOSTON MA 02115 USA

Squirrel monkeys responded under a 2-component fixed-ratio schedule of food presentation in which responding in 1 component was suppressed (punished) by delivery of pressurized air or electric shock after each response. Some doses of pentobarbital and chlordiazepoxide increased responding in the punishment component regardless of the punishing event or the level of suppression produced by those events;d-amphetamine and cocaine only decreased responding in the punishment component. Doses of each drug that markedly altered punished responding often had little effect on unpunished responding. Monkeys also responded under a 2-component fixed-interval schedule of food presentation in which responding in 1 component was punished by delivery of pressurized air. Again, some doses of pentobarbital and chlordiazepoxide, but not d-amphetamine or cocaine, increased responding in the punishment component. When local rates of responding within the 2 fixed-interval components were similar, pentobarbital and chlordiazepoxide increased punished and unpunished responding to about the same degree;d-amphetamine and cocaine selectively increased unpunished responding. These results apparently confirm those observed previously with electric shock, and suggest that the effects of drugs on punished responding are largely independent of the nature of the punishing event.

关键词：气压氯氮|艹卓|/药理学可卡因/药理学条件反射操作式/药物作用右苯丙胺/药理学剂量效应关系药物电休克类人猿亚目戊巴比妥/药理学惩罚强化分级表松鼠猴属动物男(雄)性

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The effects of high-dose methamphetamine in the aging rat: Differential reinforcement of low-rate 72-s schedule behavior and neurochemistry

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第3期294卷 850-863页

作者： Sabol, KE Richards, JB Yung, K Univ Mississippi Dept Psychol University MS 38677 USA Univ Mississippi Dept Pharmacol University MS 38677 USA W Virginia Univ Dept Psychol Morgantown WV 26506 USA

High-dose methamphetamine (METH) causes damage to the dopamine and serotonin neurons in the brains of laboratory animals. The purpose of this report was to determine the longterm consequences of high-dose METH treatment on behavior and neurochemistry. Rats were trained on the differential reinforcement of low-rate 72-s (DRL 72-s) schedule of reinforcement. Twelve weeks after training began (age 23 weeks), they received one or three high-dose METH regimens. Each regimen consisted of four injections of 15 mg/kg, at 2-h intervals. Each regimen was separated by 7 weeks. A second group received METH treatment at age 23 weeks, but behavioral training was not initiated until the rats reached age 60 weeks. A third group received METH treatment without behavioral training. DRL behavior showed mild impairments 3 to 18 weeks after the onset of treatment;the impairments did not persist into middle age. At age 70 weeks, serotonin concentrations were decreased in somatosensory cortex, occipital cortex, and hippocampus but not in other subcortical structures. Serotonin tissue concentrations were enhanced in septum and striatum but only in rats receiving three regimens and behavioral training, Dopamine was not depleted at age 70 weeks. In three additional groups, one, two, or three METH regimens were administered, and tissue concentrations were measured 6 weeks after the last treatment (corresponding to the times of the behavioral test blocks in the DRL experiments). Serotonin depletions were noted in cortex, hippocampus, amygdala, and striatum but not in septum, hypothalamus, nucleus accumbens/olfactory tubercle, or ventral midbrain. Dopamine was decreased in striatum and septum but not in nucleus accumbens/olfactory tubercle, amygdala, hypothalamus, or ventral midbrain. DRL 72-s schedule impairments are attributed to serotonin depletions. Three METH regimens did not result in greater behavioral or neurochemical deficits than one regimen.

关键词：衰老/代谢衰老/生理学行为动物/药物作用脑/解剖学和组织学脑/代谢条件反射操作式/药物作用多巴胺/代谢剂量效应关系药物甲基苯丙胺/投药和剂量甲基苯丙胺/药理学大鼠 Sprague-Dawley 强化分级表血清素/代谢温度动物男(雄)性大鼠

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ATTENUATION OF RESPONSE INHIBITION DEFICITS IN MENTALLY-RETARDED BY PROVIDING AN EXTERNAL CUE

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JOURNAL OF GENERAL PSYCHOLOGY 1976年第2期95卷 193-199页

作者： MADLE, RA RIGHTMYER, JF LAURELTON STATE SCH & HOSP LAURELTONPA 17835

SummarySummaryAn experiment was performed to assess the effects of mental age (MA) and external cues on response inhibition in the mentally retarded. TwelveSs were presented with an experimental task which required that they withhold responding for five or more seconds before pressing a key to obtain reinforcement. For half theSs the key was lighted (cued) during the waiting interval, while it was unlighted (uncued) for the other half. The results indicate that (a) response inhibition increased withMAand (b)MAdifferences might have been due to an inability to mediate the delay interval. The results were interpreted in terms of possible mediating mechanisms and implications for training inhibitory performance in the mentally retarded.

关键词：提示冲动行为/预防和控制抑制(心理学) 精神发育迟滞/治疗反应时间强化分级表标记奖酬法成年人女(雌)性人类

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ACTIVITY IN CHRONIC-SCHIZOPHRENIC PATIENTS - COMPARISON OF PIMOZIDE WITH FLUPHENAZINE IN A DOUBLE-BLIND TRIAL

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PSYCHOLOGICAL MEDICINE 1975年第2期5卷 161-164页

作者： SIMS, ACP BURNSIDE, IG ALL SAINTS HOSP BIRMINGHAM B18 5SDENGLAND

A double-blind crossover trial was carried out comparing pimozide with fluphenazine. The effects of the drugs on the activity of 20 chronic inert male schizophrenic patients were measured using nursing observations, psychiatric rating, and an operant conditioning method. When activity was assessed in these different ways, no significant difference was found between the two drugs on any of the measures. It is concluded that pimozide does not effectively increase the activity in such patients. It is considered that the free operant conditioning method used was shown to be a useful measure for comparing therapy in chronic schizophrenic patients.

关键词：投药口服慢性病条件反射操作式/药物作用氟奋乃静/投药和剂量氟奋乃静/治疗应用交谈心理学运动活动/药物作用匹莫齐特/投药和剂量匹莫齐特/治疗应用精神病状态评定量表心理学试验反应时间/药物作用强化分级表精神分裂症/药物疗法时间因素人类男(雄)性中年人

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Oral cocaine pharmacokinetics and pharmacodynamics in a cumulative-dose regimen: Pharmacokinetic-pharmacodynamic modeling of concurrent operant and spontaneous behavior within an operant context

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期295卷 634-643页

作者： Lau, CE Sun, L Wang, Q Simpao, A Falk, JL Rutgers State Univ Dept Psychol Piscataway NJ 08854 USA Rutgers State Univ Dept Chem Piscataway NJ 08854 USA Capital Univ Med Sci Sch Basic Sci Dept Chem Beijing Peoples R China

Despite wide use of cumulative-dosing procedures to evaluate dose-response relations, limited attention has been paid to investigating drug concentration-effect relations. We first characterized the pharmacokinetic (PK) parameters for i.v. (2 mg/kg) and oral cocaine (20 and 40 mg/kg) in rats. Cocaine's concentration-time profile for the escalating cumulative-dose regimen was simulated from PK parameters, dose size (1, 2, 7, 20, and 45 mg/kg by the oral route), and dosing interval (tau, 35 min) as well as validated from blood sampling at various time points. This concentration-time profile was integrated with pharmacodynamic (PD) profiles of differential reinforcement of low rate performance and spontaneous activity (large and small movements) under a differential reinforcement of low rate 45-s schedule. Effects on three behavioral measures were characterized by integrated PK-PD models using the sigmoid E-max (for increases in shorter response rate or large movements) and inhibitory E-max (for decreases in density of reinforcement) models. But for the intrinsic differences in baseline and efficacy values among the behavioral endpoints, one set of PD parameters (i.e., potency and Hill factors) predicted concentration-effect relations for the three behavioral indices across all five doses. Concurrent monitoring of operant and spontaneous activity behavior within an operant context provides a novel behavioral paradigm to investigate drug effects on spontaneous activity under conditions where a behavioral contingency exists. Additionally, a cumulative-dosing procedure is efficient for determining the entire dose-response relation and provides an ideal mode to study phenomena such as sensitization or tolerance by varying dose size and/or tau.

关键词：投药口服行为动物/药物作用可卡因/血液可卡因/药代动力学可卡因/药理学条件反射操作式剂量效应关系药物模型生物学运动活动/药物作用大鼠 Sprague-Dawley 强化分级表动物男(雄)性大鼠

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Effects of ethanol on working memory and attention in pigeons

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期293卷 551-558页

作者： Dayer, CA Baron, S Light, KE Wenger, GR Univ Arkansas Med Sci Dept Pharmacol & Toxicol Little Rock AR 72205 USA Univ Arkansas Med Sci Dept Pharmaceut Sci Little Rock AR 72205 USA

To determine whether the effects of ethanol on working memory are mediated by a secondary effect on attention, dose-response curves for ethanol were determined in eight pigeons trained under a titrating matching-to-sample (TMTS) procedure, in eight pigeons trained under a discrete-trial measure of attention, and in eight pigeons trained under a continuous-trial measure of attention. Ethanol decreased accuracy under the TMTS procedure following the three highest doses (1, 1.8, and 3 g/kg). Only the highest dose (3 mg/kg) decreased rates of responding. Attention, as measured under the discrete-trial procedure, was affected only by the two highest doses (1.8 and 3 g/kg). The 3-g/kg dose caused significant decreases in the probability of a hit and probability of a correct rejection, as well as significant increases in the probability of an error of omission and response latencies. Sensitivity to the signal decreased following 1.8 and 3 g/kg ethanol. Under the continuous-trial procedure, ethanol caused a peak in false alarms after the 1.8-g/kg dose, decreased the probability of a hit following the 1.8- and 3-g/kg doses, and increased probability of a miss at all doses. Sensitivity to the signal was not affected. A comparison of the dose-response curves for the TMTS procedure and the two measures of attention revealed that working memory (TMTS) was decreased by a lower dose than that affecting attention. This suggests that the effects of ethanol on working memory are not mediated by the subject's ability to pay attention to stimulus changes in the environment.

关键词：算法注意力/药物作用中枢神经系统抑制药/血液中枢神经系统抑制药/药理学鸠鸽科条件反射操作式/药物作用剂量效应关系药物乙醇/血液乙醇/药理学记忆短时/药物作用精神运动性行为/药物作用强化分级表信号检测(心理学)/药物作用动物男(雄)性

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Rats selectively bred for responsiveness to 5-Hydroxytryptamine_1A receptor stimulation:: Differences in differential reinforcement of low rate 72-second performance and response to serotonergic drugs

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第1期292卷 104-113页

作者： Cousins, MS Vosmer, G Overstreet, DH Seiden, LS Univ Chicago Dept Pharmacol Chicago IL 60637 USA Univ Chicago Dept Physiol Sci Chicago IL 60637 USA Univ N Carolina Sch Med Ctr Alcohol Studies Chapel Hill NC 27599 USA Univ N Carolina Sch Med Dept Psychiat Chapel Hill NC 27599 USA

High (+/-)-8-hydroxy-dipropylaminotetralin HBr (8-OH-DPAT) sensitive (HDS) rats and low 8-OH-DPAT-sensitive (LDS) rats were selectively bred for differences in sensitivity to the hypothermic effect of the 5-hydroxytryptamine(1A) (5-HT1A) receptor agonist 8-OH-DPAT in 30 to 35-day-old rat pups. These rats were trained on the differential reinforcement of low rate 72-s operant schedule. On this schedule, LDS rats had a higher response rate and a lower reinforcement rate than HDS rats. Drugs with primary action on the 5-HT system, 8-OH-DPAT, ketanserin, and fluoxetine, decreased response rate of HDS and LDS rats but increased the reinforcement rate of only the LDS rats. However, a drug with primary action on the norepinephrine system, desipramine, decreased response rate and increased reinforcement rate of HDS and LDS rats, suggesting that norepinephrine function was similar in the two lines of rats. The finding with desipramine indicates that increases in reinforcers on the differential reinforcement of low rate 72-s task are not simply dependent on baseline response or reinforcement rate. We also observed that 8-OH-DPAT engenders a greater hypothermic response in adult (90-day-old) HDS rats than in adult LDS rats. The 5-HT1A receptor antagonist WAY-100635 antagonized the hypothermic response. Tissue levels of 8-OH-DPAT from several brain regions in LDS and HDS rats did not differ from each other at either 15- or 30-min postinjection. Because the LDS and HDS rats have different responses to 5-HT-acting drugs, these rats may be useful for studying the role of the serotonergic system in depression.

关键词： 8-羟-2-(二-n-丙胺)四氢萘/分析 8-羟-2-(二-n-丙胺)四氢萘/药理学肾上腺素能摄取抑制剂/药理学年龄因素行为动物/药物作用生物源单胺类/分析脑化学/药物作用条件反射操作式地昔帕明/药理学剂量效应关系药物药物相互作用氟西汀/药理学低温/化学诱导酮色林/药理学受体血清素/分类受体血清素/药物作用强化分级表血清素激动药/药理学血清素拮抗药/药理学血清素摄取抑制药/药理学时间因素动物男(雄)性大鼠

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MODIFICATION OF SELF-DISCLOSING BEHAVIORS THROUGH MODELING AND VICARIOUS REINFORCEMENT

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JOURNAL OF GENERAL PSYCHOLOGY 1976年第2期95卷 209-218页

作者： FANTASIA, SC LOMBARDO, JP WOLF, TM SUNY COLL CORTLAND DEPT PSYCHOLCORTLANDNY 13045 SUNY COLL CORTLAND CORTLANDNY 13045

SummarySummaryModeling techniques were used to model moderate disclosure to high and low disclosers. Eighty female undergraduates (40 low disclosers and 40 high disclosers) listened to a model select items that were rated as moderate disclosures for discussion. Two modeling conditions were employed; in one condition the model was reinforced by theE(vicarious reinforcement), in the second condition the model was not reinforced. Two control conditions, one with the model present, the other with the model absent were also included. The results of two separate 2 × 4 × 2 repeated measures, hierarchical analyses of variance on the subject distance from modeled intimacy, and the number of moderate items selected on pre- and posttests, indicated that both modeling conditions were successful in producing moderation of self-disclosure.

关键词：行为疗法模仿行为强化分级表自我概念自我揭露社会适应女(雌)性人类

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EFFECT OF INTRACEREBROVENTRICULAR BRADYKININ AND RELATED PEPTIDES ON RABBIT OPERANT-BEHAVIOR

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 1975年第1期193卷 1-10页

作者： MELO, JC GRAEFF, FG FAC MED RIBEIRAO PRETO DEPT PHARMACOL SAO PAULO BRAZIL

The dose-effect relationships of intraventricularly injected bradykinin, Gly-Arg-Met-Lys-bradykinin (GAML-bradykinin), synthetic substance P and angiotensin II on lever-lifting behavior of rabbits in a variable-interval (VI) 72-second schedule of sweetened water presentation were determined. All peptides used caused dose-dependent decreases in overall rates of VI responding during the experimental session in the following order of potency: angiotensin II greater than bradykinin = substance P greater than GAML-bradykinin. The angiotensin II dose-effect curve was less steep than those of the other peptides. The administration of nearly equimolar doses of the bradykinin potentiating peptides, BPP5a and BPP9a, slightly decreased overall VI response rates and caused a 10- to 20-fold potentiation of the rate-decreasing effect of bradykinin on VI responding. Both angiotensin II and bradykinin caused pauses in responding of dose-dependent duration at the beginning of the experimental session that were followed by normal VI responding. The effect of GAML-bradykinin on VI performance was similar to that of bradykinin and angiotensin II but had a delay of onset of 3 to 6 minutes. In contrast, substance P caused actual decreases in response output and pauses of variable duration interspersed between periods of regular VI responding. At the doses used, both bradykinin-potentiating peptides caused uniform decreases in VI responding throughout the experimental session. Gross behavioral changes caused by the peptides were also observed. After the intraventricular injection of bradykinin or GAML-bradykinin, rabbits showed decreased motility, ptosis, miosis and lowered ears; after angiotensin II, animals remained motionless but with wide open eyes, fully raised ears and no miosis. In turn, substance P caused restlessness and increased locomotion. These results together with reported evidence on other powerful central actions of bradykinin, angiotensin and substance P and on the exist

关键词：血管紧张素Ⅱ/药理学行为动物缓激肽/投药和剂量缓激肽/类似物和衍生物缓激肽/药理学脑室条件反射操作式/药物作用注射肽类/投药和剂量肽类/药理学强化分级表立体定位技术动物男(雄)性兔

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CASE-STUDY - USE OF DIFFERENTIAL REINFORCEMENT TO SUPPRESS SELF-INJURIOUS AND AGGRESSIVE-BEHAVIOR

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PSYCHOLOGICAL REPORTS 1976年第3期39卷 843-849页

作者： FRANKEL, F MOSS, D SCHOFIELD, S SIMMONS, JQ UNIV CALIF LOS ANGELES LOS ANGELESCA 90024

A program of differential reinforcement of other behavior was employed to reduce the rates of aggression and head-banging in a 6-yr., 8-mo.-old profoundly retarded female. Whereas, two different time-out procedures were not associated with stable decreases in aggressive behavior, this program was associated with immediate and dramatic decreases in aggression and head-banging. The present results suggest that (a) initial values of such programs may be situation-specific and (b) either the procedure or the inclusion of contingencies for all maladaptives within one program may be superior to a time-out program which focuses on a subset of all maladaptive behavior.

关键词：攻击行为疗法条件反射操作式随访研究精神发育迟滞/并发症强化分级表自残/并发症自残/预防和控制儿童女(雌)性人类

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