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Biomedical subjects

R L Balster

Publications and source records attributed to R L Balster.

At least 19 recordsLinked to original sources
PubMed1979

Tolerance to the behavioral effects of phencyclidine: the importance of behavioral and pharmacological variables.

The effects of phencyclidine (PCP) on the behavior of rats responding to a fixed-interval 1 min schedule of water delivery were determined before, during, and after a period of daily PCP injections. The effects of acute PCP on overall response rate were biphasic: low doses increased and high doses decreased rates. In addition, PCP produced a dose-related decrease in quarter-life and high doses of PCP decreased the number of reinforcers delivered. During the daily injection regimen roughly a two-fold tolerance developed to the effects of 8.0 mg/kg PCP on response rate in animals receiving either presession or post-session injections of this dose, emphasizing the predominance of pharmacological variables in PCP tolerance. However, slight differences between these groups in tolerance development and in the rate of tolerance loss demonstrate that behavioral variables can influence tolerance to the behavioral effects of PCP.

Animals↗
PubMed1979

Opioids: similarity between evaluations of subjective effects and animal self-administration results.

Abuse potential studies of 33 morphine-like analgesics were compared in humans and monkeys. The results of intravenous self-administration studies in rhesus monkeys were correlated with measures of morphine-like signs, symptoms, and subjective effects in ex-addicts. Each set of data was assigned to a position in a 3 x 3 contingency table dependent upon whether the results were yes, no, or equivocal. Of the 33 drugs, 29 were given identical classifications in both the human and animal test procedures. This good concordance between the human and animal results further validates each procedure and suggests the possibility that both the human and animal procedures are measuring a common underlying pharmacological property which relates to abuse potential of drugs.

Animals↗
PubMed1979

Rapid substitution procedure for intravenous drug self-administration studies in rhesus monkeys.

Rhesus monkeys were trained to press a lever one hundred times (FR 100) to obtain either a food pellet or an intravenous drug injection. Two daily experimental sessions, one in the morning and one in the afternoon, were divided into three 15 minute periods each. In Periods 1 and 3 lever pressing behavior was maintained by the delivery of food. Period 2 lever pressing was maintained by the intravenous injection of a drug solution. The drug available each day followed a four day sequence of cocaine (30 microgram/kg/injection), saline (1.0 ml/injection), cocaine, and test compound. This four day sequence was repeated to test a series of 16 psychoactive compounds at two doses each. These drugs were compared to saline for their ability to maintain Period 2 responding during the afternoon session. Morphine, oxymorphone, codeine, pentazocine, d-amphetamine and methylphenidate all maintained responding at rates significantly greater than for saline. Cyclazocine, naloxone, levallorphan, scopolamine, chlorpromazine, fenfluramine, and (+/-)-9-nor-9-alpha-hydroxy-hexahydrocannabinol (alpha-HHC) did not maintain responding during Period 2. The results with procaine, beta-HHC and nalorphine were considered equivocal. The authors suggest the use of a rapid substitution procedure as a method of initial screening of drugs with potential reinforcement efficacy.

Animals↗
PubMed1979

Effects of phencyclidine, d-amphetamine and pentobarbital on spaced responding in mice.

The effects of acute IP administration of phencyclidine (PCP), d-amphetamine (AMPH) and pentobarbital (PB) were determined in 10 mice trained to lever press on a differential reinforcement of low rate 10 sec schedule of sweetened milk presentation. The effects of PCP were highly consistent, with large response rate increases (and a corresponding shift toward shorter interresponse times) at doses of 1 and 3 mg/kg. Higher doses generally decreased response rates and resulted in a bimodal interresponse time distribution. The effects of AMPH were similar to PCP but less consistent. Although some of the subjects showed substantial response rate increases at doses between 0.3 and 10 mg/kg, half of the subjects did not show increased response rates at any dose. The effects of AMPH on the interresponse time distribution were similar to PCP. The effects of PB were least like those of PCP. The effect in most subjects was to produce a dose-related decrease in response rate and a flattening of the interresponse time distribution. Occasional small response rate increases were observed with PB.

Animals↗
PubMed1979

Reinforcing properties of some local anesthetics in rhesus monkeys.

The reinforcing properties of several local anesthetics were determined in rhesus monkeys experienced in the intravenous self-injection of cocaine. Intravenous procaine and, occasionally, tetracaine maintained response rates higher than did vehicle injections in most monkeys. In contrast, lidocaine, procainamide and diethylaminoethanol (a metabolite of procaine) failed to maintain responding resulting in their intravenous delivery. These results demonstrate that not all local anesthetics are positive reinforcers in the rhesus monkey when delivered intravenously. Furthermore, the reinforcing properties of procaine probably cannot be attributed to its metabolite diethylaminoethanol. The data suggest that short-acting, esteratic local anesthetics are most likely to have reinforcing properties in the rhesus monkey.

Anesthetics, Local↗
PubMed1979

Effects of phencyclidine, atropine and physostigmine, alone and in combination, on variable-interval performance in the squirrel monkey.

The role played by cholinergic activity in the effects of phencyclidine (PCP) on schedule-controlled responding was studied in three squirrel monkeys trained to respond on a variable-interval (VI) 100 sec schedule of food presentation. A low dose of PCP (0.08 mg/kg IM) produced small increases in rates of responding. Higher doses (0.16--0.64 mg/kg) produced dose-dependent decreases in rates of responding. Atropine (0.05--3.2 mg/kg IM) and physostigmine (0.025--0.20 mg/kg IM) caused only decreases in response rates, the dose-response curve for atropine being particularly flat over a wide range of doses. When atropine was combined with PCP, no significant interaction was obtained. When physostigmine was combined with PCP, a complex interaction was observed. Evidence fo partial antagonism of PCP by physostigmine was obtained only at the highest PCP dose tested. Atropine-physostigmine combinations resulted in response rates suggestive of antagonism.

Animals↗
PubMed1979

Effects of systemic and intraventricular administration of cannabinoids on schedule-controlled responding in the squirrel monkey.

The effects of a number of cannabinoids in squirrel monkeys trained to respond on a chain fixed-interval fixed-ratio schedule of food presentation were determined after intraperitoneal (i.p.) and intraventricular (i.v.t.) administration. The order of potency was (+/-)-9-nor-9 beta-OH hexahydrocannabinol, 11-OH-delta 9-tetrahydrocannabinol, delta 9-tetrahydrocannabinol (delta 9-THC), cannabinol and cannabidiol. (+/-)-9-Nor-9 alpha-OH-hexahydrocannabinol was inactive at doses up to 3 mg/kg i.p. and 0.1 mg/kg i.v.t. Although the order of potency was the same by both routes of administration, the i.v.t./i.p. potency ratio differed markedly. This demonstrates the importance of route of administration in assessing structure-activity relationships of cannabinoids and suggests that differences in penetration to the central nervous system may be an important determinant of behavioral activity. Although 11-OH-delta 9-THC was more potent than the parent compound delta 9-THC by both routes, the potency difference was less after i.v.t. administration. It was also demonstrated that metabolic conversion of [3H]delta 9-THC does not take place in squirrel monkey brain when administered i.v.t. which could account for the direct i.v.t. effects of delta 9-THC. These observations suggest that metabolic conversion of delta 9-THC in the liver is not necessary for its behavioral effects.

Animals↗
PubMed1979

Behavioral teratology evaluation of trichloromethane in mice.

Trichloromethane (TCM) has been identified as an important contaminant of drinking water. TCM was evaluated for possible behavioral effects in the offspring of mice treated throughout the reproductive period. Male and female albino mice were gavaged with vehicle (Emulphor: saline) or 31.1 mg/kg/day for 21 days prior to mating, throughout mating (21 days or until a vaginal plug was detected) and the dam was continued with daily gavage throughout gestation and lactation. The pups were also gavaged daily with the same dose beginning on Day 7. Five TCM and five control litters were used for this study. On the day of birth each litter was reduced to 8 pups. For the next 15 days, 3 pups from each litter were randomly selected each day for evaluation on a battery of tests of neurobehavioral development. The scoring system for this test battery was developed for this study. On Day 17 motor performance for all pups was evaluated using the latency to right themselves on an inverted screen. On Days 22 and 23 they were evaluated on a one-trial passive avoidance learning task. No consistent significant differences were observed in any of the measures between TCM and vehicle treated groups.

Aging↗
PubMed1978

Choice behavior in rhesus monkeys: cocaine versus food.

Rhesus monkeys were allowed to choose between intravenous injections of cocaine and food reinforcement for lever pressing. A choice trial was available every 15 minutes continuously for 8 days. The animals chose cocaine almost exclusively, which resulted in high cocaine intake, decreased food intake, weight loss, and marked behavioral toxicity. The study provides evidence of the reinforcing efficacy of cocaine.

Animals↗
PubMed1978

The effects of phencyclidine on amphetamine stereotypy in rats.

In two separate experiments a 9 point rating scale was used to assess the effects of various doses of phencyclidine on the behavioral stereotypy produced by d-amphetamine in rats. A dose of phencyclidine (2.5 mg/kg) which had no effect when given alone, enhanced the behavioral effects of 1 and 3 mg/kg of d-amphetamine. Higher dises (5 and 10 mg/kg) of phencyclidine produced some stereotypy when given alone but they also produced ataxia which confounded the rating of their other behavioral effects. These higher doses did not enhance the effects of d-amphetamine. This study provides further evidence that phencyclidine may have dopaminergic activity similar to amphetamine.

Animals↗
PubMed1978

Effects of combinations of phencyclidine and pentobarbital on schedule-controlled behavior in the squirrel monkey.

Three squirrel monkeys trained on a variable interval schedule of food presentation were used to examine the interaction between phencyclidine (PCP) and pentobarbital (PB). First, dose-response curves for each drug given alone were obtained. PCP caused small response rate increases at low doses, and a dose-dependent decrease in responding at higher doses. PB caused only dose-dependent decreases in responding. The PB dose-response curve was then redetermined in the presence of four doses of PCP. Little support was found for the hypothesis that PCP enhances the depressant properties of PB. In fact, most dose combinations caused less disruption of responding than expected from simple addition of the effects of each drug given alone. These results are discussed in terms of species differences, measurement of different dipendent variables and rate-dependency.

Animals↗
PubMed1978

The effects of acute and chronic phencyclidine on schedule-controlled behavior in the squirrel monkey.

The effects of acute and chronic administration of phencyclidine (PCP) were examined in five male squirrel monkeys trained to respond on a chain fixed-interval fixed-ratio schedule of food presentation. Acute PCP (0.01-0.60) mg/kg i.m.) produced dose-related decreases in response rate during both components of the schedule. Both components were equally affected by the drug. The effects of the drug on fixed-interval response rate were dependent on the control rate of responding in corresponding segments of the interval. After the initial dose-response determination, the subjects were placed on an individualized regimen of chronic PCP administration lasting from 82 to 126 days, beginning with daily injections for 2 days alternating with saline injections for 2 days, progressing to four injections daily. No evidence of physical dependence was seen upon withdrawal of the drug. Redetermination of the dose-response function for PCP (0.03-1.0 mg/kg i.m.) demonstrated a nearly 2-fold shift to the right of both the fixed-interval and fixed-ratio dose-response curves, indicating tolerance. In addition, the subjects' behavior recovered sooner from a dose of PCP (0.60 mg/kg i.m.) given after the chronic regimen than from the same dose given before the chronic regimen. The results demonstrate that tolerance can occur to the behavioral effects of PCP in the squirrel monkey.

Animals↗
PubMed1977

Reinforcing properties of intravenous procaine in rhesus monkeys.

The lever pressing behavior of rhesus monkeys was maintained by a fixed ratio 10 schedule of intravenous cocaine (3 monkeys) or codeine (2 monkeys) injections during 2 hour sessions. Saline or various doses of procaine hydrochloride were substituted for the baseline reinforcer for 6 consecutive sessions. Each substitution was separated by 3 or more days of cocaine or codeine reinforced responding. At one or more doses, procaine substitution resulted in response rates higher than saline control in all 5 animals. High response rates (greater than 30 injections per session) were obtained in 4 of the 5 monkeys. In addition, procaine self-administration was studied in two naive monkeys given 23 hour per day access to procaine following an initial 10 days of saline contingent operant level responding. At a dose of 0.3 mg/kg/injection, both animals initiated responding for procaine reinforcement. Drug intake varied widely from day to day, however each animal took over 1200 injections per day (over 360 mg/kg) at least once during the 30 days of access. With the exception of decreased food intake, there was little evidence for behavioral toxicity from these doses. Following a second 10 days of saline self-administration, both animals were given access to 3.0 mg/kg/injection procaine. A substantially greater intake of procaine was observed which was associated with marked toxicity.

Animals↗