Search PubMed⌕ Search

Biomedical subjects

R R Griffiths

Publications and source records attributed to R R Griffiths.

214 records · Page 12Linked to original sources

Relationship between anorectic and reinforcing properties of appetite suppressant drugs: implications for assessment of abuse liability.

A quantitative ratio measure was developed which permitted comparisons between the reinforcing and anorectic potency of eight phenylethylamine anorectics and cocaine in laboratory baboons. The ordering of these compounds based upon this ratio bears a reasonable correspondence to clinical drug evaluations. The measure may provide information for preclinical evaluation of relative abuse potential of anorectic drugs.

Animals↗

Drug-produced changes in human social behavior: facilitation by d-amphetamine.

The effects of oral d-amphetamine 5-30 mg on human social and verbal behavior were studied using repeated observations within subjects under a time-sampling observation procedure in a residential research ward. d-Amphetamine increased socializing in all three subjects studied, but only increased standing in one of the subjects. In the second experiment throat microphones and voice-operated relays were used to measure automatically quantitative aspects of dyadic verbal interactions during 1-hr daily sessions. Total speaking time showed dose-related increases in 5 of the 7 subjects receiving d-amphetamine. Adjective checklist self-report scores indicating stimulant drug effects were as sensitive and reliable as the speaking measure to the effects of d-amphetamine in these subjects. Speaking time also increased in 2 of the 8 partners who received placebo when the subjects with whom they were paired received d-amphetamine. This represents a socially mediated indirect drug effect. Adjective checklist scores of the partners receiving placebo were not changed when the paired subjects received d-amphetamine. Under controlled experimental conditions the naturalistic human behaviors of socializing and speaking are sensitive dependent variables for behavioral pharmacology research.

Adult↗

Comparison of behavior maintained by infusions of eight phenylethylamines in baboons.

Doses of eight phenylethylamines were substituted for cocaine on a drug-maintained behavior baseline in baboons. Intravenous infusions of drug were contingent upon completion of 160 lever presses (a 160-response fixed-ratio schedule; FR 160). A 3-h time-out period followed each infusion, permitting a maximum of 8 infusions per day. Fenfluramine was the only drug that did not maintain self-infusion performance at any dose tested. d-Amphetamine was approximately 10 times more potent than phentermine, phenmetrazine or diethylpropion, and 20 to 30 times more potent than methylenedioxyamphetamine (MDA), clortermine or chlorphentermine, in maintaining self-infusion behavior. Some doses of d-amphetamine and phentermine produced a cyclic pattern of drug intake over days. Increasing self-infused doses of all drugs produced a substantial suppression of concurrent food-maintained behavior. There was no clear relation between the potency of the phenylethylamines in maintaining self-infusion performance and the potency in suppressing food-maintained behavior which indicates that different mechanisms may underlie the two effects. Examination of chemical structures indicates that substitution on the phenyl ring may decrease the potency of phenylethylamines in maintaining self-infusion behavior.

3,4-Methylenedioxyamphetamine↗

Surgical anatomy of the ascending ramus of the mandible.

A study of identifying the position of the lingula of the mandible on the external surface is described. The study was undertaken in an attempt to avoid damage to the inferior dental neurovascular bundle during operative procedures on the ascending ramus.

Humans↗

Effects of response requirement upon human sedative self-administration and drug-seeking behavior.

Five male volunteers with histories of sedative drug abuse were given the opportunity to self-administer up to 20 oral doses per day of either diazepam (10 mg per dose) or sodium pentobarbital (30 mg per dose). Each dose was purchased with tokens earned by exercising on a stationary exercise bicycle. Each two minutes of exercise earned one token. In a mixed order across days the number of tokens required to purchase each dose was varied among 1, 3, 5, 8 and 10. Drug intake decreased as a function of increased response requirement for purchasing the drug. Response output for drug tended to be an inverted-U shaped function of the response requirement. Thus, the cost of drug doses act as a powerful environmental influence upon both of these aspects of drug abuse behavior - amount of drug consumed and amount of drug-seeking behavior.

Adult↗

Facilitation of human tobacco self-administration by ethanol: a behavioral analysis.

The effect of ethanol on the cigarette smoking of alcoholic subjects was studied in a residential laboratory. During daily 6-hr sessions, cigarettes were obtained either by request to the ward staff or by operation of a lever (fixed-ratio 5 or 10). In a mixed sequence across days, sessions involved ingestion of either vehicle (orange juice or vehicle plus ethanol (133.7 g). During ethanol sessions, the rate of cigarette smoking increased from 26% to 117% of vehicle levels. A series of control studies eliminated a number of potential behavorial mechanisms for the observed effect and indicated that the ethanol-induced increase in cigarette smoking occurred under a variety of experimental conditions: (1) when smoking could not occur concurrently with ethanol or vehicle consumption; (2) when subjects were not allowed to socialize; (3) when ingestion of ethanol or vehicle was scheduled for a number of consecutive days; (4) when various doses of ethanol were administered under blind conditions. In control experiments, weighing unsmoked tobacco and counting the number of puffs per cigarette indicated the effect was not due to smoking less of each cigarette. The effect was not limited to the experimental sessions alone, since total daily smoking was higher on ethanol days than vehicle days.

Adult↗

Behavioral procedures for evaluating the relative abuse potential of CNS drugs in primates.

Laboratory animal drug self-administration procedures for evaluating pharmacological abuse potential have focused on performance measurements involving relative rates of drug-maintained responding, discrete-trial choice determinations, and response cost or progressive ratio values. Relative rate measures have proved historically difficult to use for reliable reinforcement strength determinations. Discrete-trial choice procedures for assessing the relative reinforcing properties of stimulus events have recently been reported to effectively discriminate between different drugs and different doses of the same drug. Additionally, response cost or progressive ratio procedures involving systematic increases in the number of responses required for successive drug reinforcements have begun to reveal orderly relationships between different reinforcing drugs at various doses and a "breaking point" measure of the relative strength of a reinforcer. Comparisons between selected doses of cocaine, methylphenidate, and secobarbital with a series of five baboons using this procedure have shown that over the same behaviorally active dose range, cocaine breaking points were higher than all of the breaking points obtained with methylphenidate. Dose-response differences were also revealed in "breaking point" comparisons between secobarbital on the one hand, and methylphenidate and cocaine, on the other.

Animals↗

Human sedative self-administration: effects of interingestion interval and dose.

In a residential hospital ward setting, either sodium pentobarbital, diazepam or ethanol was made availabe for oral ingestion to volunteer human subjects with documented histories of drug abuse. During specified portions of the day, tokens could be earned by riding an exercise bicycle and exchanged for doses of a drug. Increases in the required minimum interingestion interval from 0 to 30 minutes produced decreases in the number of ingestions of sodium pentobarbital and diazepam. In another experiment, increases in the dose per ingestion (30-90 mg of sodium pentobarbital, 2-10 mg of diazepam, or 1.86-11.14 g of ethanol) produced increases in the number of ingestions. In both experiments, the effects of the manipulated variable were similar for all of the drugs studied. The study demonstrates the feasibility of human self-administration research with the sedative drugs, sodium pentobarbital and diazepam, for which substantive experimental data have not previously been reported. In addition, the results indicate that both dose and minimum interingestion interval bear a systematic controlling relationship to the occurrence of drug self-administration behavior.

Adult↗

Comparison of progressive-ratio performance maintained by cocaine, methylphenidate and secobarbital.

Cocaine, methylphenidate and secobarbital were compared on a drug maintained progressive-ratio procedure in baboon subjects. Trials, scheduled throughout the day, occurred at a minimum interval of 3 hrs after completion of the preceding trial. A ratio response requirement on the "initiate" lever was required during each trial which terminated in a single intravenous infusion of drug. A drug was introduced on the progressive-ratio procedure with a low ratio requirement in order to obtain a baseline performance of a high stable frequency of trial completion. The ratio requirement was systematically increased every 7 days until the "breaking point" when the rate of completing trials fell below a criterion level. Within-subject comparison revealed that cocaine produced higher breaking points than methylphenidate at the same absolute dose, 0.4 mg/kg. At the range of doses studied, manipulation of doses of methylphenidate (0.1-0.8 mg/kg) and cocaine (0.4-1.6 mg/kg) had little effect on breaking point. In contrast, increasing doses of secobarbital (6.0 and 12.0 mg/kg) produce higher breaking points within the same subjects.

Animals↗