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Biomedical subjects

R L Balster

Publications and source records attributed to R L Balster.

At least 181 records · Page 10Linked to original sources
PubMed1982

Unlimited access intravenous drug self-administration in rhesus monkeys.

Rhesus monkeys implanted with intravenous catheters readily self-inject a wide variety of psychoactive drugs. Under conditions where access to drug is not limited, pharmacological variables are important determinants of the rate and pattern of drug-reinforced responding. Data for unlimited access phencyclidine self-administration are presented to illustrate the types of findings obtained from unlimited access studies. The results with phencyclidine indicate a pattern of drug intake that progressed from variable day-to-day response rates at a low dose to relatively stable daily response rate with greater drug intake at a higher dose. The pattern of responding, toxicity, and development of physical dependence seen in these subjects were similar in many respects to results found with several other drugs under conditions of unlimited access. These findings demonstrate that unlimited access studies are particularly useful for revealing toxic consequences of self-administered doses. Moreover, a review of the literature indicated that procedures allowing unlimited access by drug-naive monkeys were at least as likely to reveal reinforcing properties of drugs as limited access procedure using drug-experienced subjects.

Animals↗
PubMed1981

Discriminative stimulus properties of phencyclidine and five analogues in the squirrel monkey.

Squirrel monkeys were trained to discriminate 0.16 mg/kg of 1-(1-phenylcyclohexyl) piperidine (PCP) from saline in a two-lever drug discrimination task on a fixed-ratio 32 schedule of food presentation. Intramuscular injections were given 5 min pre-session in a double alternation pattern. After reliable discriminative control of lever choice was established, dose-response determinations for generalization to the training dose of PCP was made with several doses of PCP, N-ethyl-1-phenylcyclohexylamine (PCE), 1-[1-(2-thienyl)cyclohexyl] piperidine (TCP), 1-(1-phenylcyclohexyl) morpholine (PCM), 1-(1-phenylcyclohexyl) pyrrolidine (PHP), and ketamine. All drugs produced dose-dependent PCP-appropriate responding. For each analogue, a dose was found which produced stimulus control of responding comparable to that of the PCP training dose. ED50 values were determined for each drug for percent drug-lever appropriate responding and for suppression of operant responding during test sessions. The relative potency for producing drug-lever appropriate responding was: TCP greater than PCP = PCE greater than PHP greater than PCM greater than ketamine. The relative potency for suppression of operant responding was: PCP = TCP greater than PHP greater than PCE greater than PCM greater than ketamine. In all cases, the dose necessary to suppress operant responding to fifty percent of vehicle rates was three to five times larger than the ED50 dose for drug-lever appropriate responding. The results of this study indicate marked similarities in the behavioral effects of these six arylcyclohexylamines.

Animals↗
PubMed1981

Effects of antipsychotic compounds in rhesus monkeys given a choice between cocaine and food.

Chlorpromazine (CPZ) and haloperidol (H) have been suggested as possible antagonists of the reinforcing effects of psychomotor stimulant drugs. To test this hypothesis in animals, four rhesus monkeys were trained in a preference procedure to choose between intravenous injections of cocaine or food presentation. Frequency of cocaine choice increased as unit dose of cocaine was increased. Continuous infusions of low or intermediate doses of CPZ or H either did not affect or increased the frequency of cocaine choice. Higher doses of CPZ or H completely suppressed responding for both reinforcers. Although ther appears to be a mutual antagonism of some of the effects of cocaine and these antipsychotic compounds, the results of the present experiment fail to support the hypothesis that the reinforcing effects of cocaine can be antagonized with CPZ or H.

Animals↗
PubMed1981

Effects of combinations of phencyclidine and pentobarbital on fixed-interval performance in rhesus monkeys.

The effects of phencyclidine (PCP, 0.1-.08 mg/kg), pentobarbital (PB, 2-32 mg/kg) and of combinations of these two drugs were determined in rhesus monkeys trained to respond on a fixed-interval 5-min schedule of food presentation. When combinations of PCP and PB were tested, dose-effect functions for PB on overall response rate were shifted to the left relative to those for PB given alone. This effect was dependent on PCP dose: the higher dose of PCP (0.2 mg/kg) shifted the PB dose-effect function further than did the lower dose (0.1 mg/kg). The effects of both drugs alone and in combination depended upon the rate of responding under control conditions. Individual drugs and combinations increased low rates of responding, increasing and then at higher doses decreased intermediate rates of responding and only decreased high rates of responding. Nevertheless, the effects of combinations of PCP and PB were always shifted to the left relative to PB given alone. This interaction was quantified by using isobolograms for those dependent measures that were decreased by the two drugs given alone or in combination. This analysis revealed that the nature of the interaction between PCP and PB depended upon the dose combination and the measure of performance. Relative to the predictions of a dose-addition model, the interaction was quantitatively greater (additive or supra-additive) when the lower dose of PCP was combined with PB.

Animals↗
PubMed1981

The effects of acute and repeated toluene exposure on operant behavior in mice.

Adult male CD-1 mice were trained on a differential reinforcement of low rate (DRL) 10-sec schedule for milk presentation during 15-min sessions. After training, an initial concentration-effect curve was determined for acute exposure to toluene (200-6400 ppm). Exposures were carried out in a static exposure chamber for 30 min; operant sessions began immediately after removal from the chamber. Mice were exposed to air under the same conditions on days they were not exposed to toluene. Response rate increases were seen at low concentrations and decreases at higher concentrations (greater than 3200 ppm). The rate of reinforcement decreased in a concentration-dependent manner. Mice were then exposed to 6000 ppm toluene for 30 min daily, 7 days a week for 7 weeks, immediately before each session. During this time the response rate was variable, but reinforcement rate remained consistently low. Following the termination of chronic toluene exposure, a second concentration-effect curve was determined which was not significantly different from the initial curve. There was, however, a nonsignificant tendency towards higher response rates at the rate-increasing concentrations. Thus after repeated exposures no tolerance to toluene was seen under these test conditions.

Animals↗
PubMed1980

Continuous-access phencyclidine self-administration by rhesus monkeys leading to physical dependence.

IV phencyclidine (PCP) self-administration was studied in five rhesus monkeys. The animals were given 23 h per day access with each respose producing an injection. For the first seven sessions saline was made contingent on responding. For the next 30 sessions responses produced 0.01 mg/kg PCP and for the next 20 sessions responses produced 0.05 mg/kg PCP. Withdrawal signs and symptoms were evaluated every 4 h during the subsequent saline-access period. All animals responded for 0.01 mg/kg injections at rates higher than their initial saline rates. Response rates decreased but total PCP intake increased during access to the higher dose. The levels of PCP self-administered resulted in severe intoxication. Evidence for physical dependence development was obtained. The symptoms emerged within 4--8 h after access was terminated, peaked at 12--16 h, and subsided by 24--48 h. The syndrome could be reversed by IV PCP administration. The most common symptoms were vocalizations, hyperresponsivity, bruxism, oculomotor hyperactivity, and diarrhea. During withdrawal the animals refused preferred food. In some of the animals piloerection, tremors, ear and facial twitches, and priapism occurred. Rhythmic abdominal contractions and emesis were seen in one subject and convulsive activity was seen in one subject.

Animals↗
PubMed1980

The effects of delta 9-tetrahydrocannabinol alone and in combination with cannabidiol on fixed-interval performance in rhesus monkeys.

It has been reported that cannabidiol (CBD) antagonizes the effects of delta 9-tetrahydrocannabinol (THC) on operant behavior in rats and pigeons. We have replicated this finding with rhesus monkeys. Four rhesus monkeys were trained to lever press on a fixed-interval 5-min schedule of food presentation with a 1-min limited hold and 1-min time out between successive intervals. The effects of 0.3 and 1.0 mg/kg THC alone were determined three times during the experiment; before the CBD-THC interaction, after the CBD-THC interaction and once with the CBD vehicle. A dose of 30 mg/kg CBD, which alone resulted in a 24% reduction in responding, completely antagonized the response rate reduction produced by 0.3 mg/kg THC. The effects of THC revealed a rate-dependent effect that did not conform to the log-linear rate-dependency plots described for most other drugs.

Animals↗
PubMed1980

Modification of the behavioral effects of phencyclidine by repeated drug exposure and body weight changes.

In the first experiment, the effects of phencyclidine (PCP) on intake of sweetened condensed milk by rats were compared before and during a period of repeated daily injections of PCP or saline. A shift to the right in the PCP dose-effect function was found in rats receiving daily PCP injections indicating tolerance development to the effects of PCP on milk intake. The dose-effect function of PCP was shifted to the right in animals receiving daily saline as well. However, when body weight changes were controlled for in this groups of animals, the effects of PCP were the same as they had been initially, implicating body weight as a determinant of the behavioral effects of PCP. In the second experiment, a direct comparison of the behavioral effects of PCP in high- and low-weight animals revealed diminished effects of PCP in high-weight animals. When these animals were treated with 3H-PCP, brain total radioactivity as well as 3H-PCP in the high-weight animals were significantly lower than those in the low-weight animals.

Animals↗
PubMed1980

Comparison of phencyclidine and three analogues on fixed-interval performance in rhesus monkeys.

The effects of four arylcyclohexylamines on operant performance in rhesus monkeys were compared. Four rhesus monkeys were trained to lever press on a multiple fixed-interval 5 min time out 1 min schedule of food presentation during daily 1 1/2 hour sessions. Dose-response curves and median effective doses were determined for phencyclidine, N-ethyl-1-phenylcyclohexylamine, 1-(1-(2-thienyl) cyclohexyl) piperidine and ketamine. Ketamine was found to be approximately 1/10 as potent as the other drugs which were approximately equipotent. The drugs had qualitatively similar effects. High doses of all four drugs decreased overall response rates and the slopes of the dose-response curves were comparable. A dose-related rate-dependent effect was found for all four drugs. Onset and duration of the drug effects were also presented.

Animals↗
PubMed1980

The effects of phencyclidine and three analogues on motor performance in mice.

A measure of motor impairment in which mice were required to climb to the top of an inverted screen was used to study the effects of phencyclidine. The time course of effects of phencyclidine after intravenous, intraperitoneal and per os administrations was compared. The intravenous route resulted in a rapid peak effect of activity and phencyclidine was most potent by this route. Peak effects of phencyclidine were seen by 30 min after intraperitoneal and per os administrations and the decline in activity was not very different with these two routes. However, greater peak effects were seen with intraperitoneal than per os administration. The effects of phencyclidine were also compared to ketamine, N-ethyl-phenylcyclohexylamine (PCE) and 1-[1-(2-thienyl)-cyclohexyl]-piperidine (TCP). The order of potency was PCE greater than phencyclidine greater than TCP greater than ketamine. PCE, phencyclidine and TCP had similar time courses of activity, whereas ketamine was shorter acting.

Animals↗
PubMed1980

Chemical and behavioral studies of 1-piperidinocyclohexanecarbonitrile (PCC): evidence for cyanide as the toxic component.

In vitro and in vivo studies of piperidinocyclohexanecarbonitrile (PCC): evidence for cyanide involvement in toxicity. The decomposition profile of piperidinocyclohexanecarbonitrile (PCC) was determined under simulated physiological conditions in vitro and in normal saline using gas chromatography. In normal saline, PCC undergoes pseudo first order decomposition with a k = 2.2 x 10(-2) min-1 (t 1/2 = 31.6 min). In 0.05 M phosphate buffer, pH 7.4 at 37 degrees C, k = 0.19 min-1 (t 1/2 = 3.7 min), and in human serum incubations, k = 0.15 min-1 (t 1/2 = 4.6 min). The median effective doses (ED50's) of PCC and NaCN for motor impairment in mice were determined using the screen test (PCC = 48.5 micrometers/kg; NaCN = 36.7 micrometers/kg). The median lethal doses (LD50's) of PCC and NaCN in mice were also determined (PCC = 133.6 micrometers/kg; NaCN = 130.6 micrometers/kg). Observations of the behavioral effects and gross appearance of the animals after NaCN and PCC injections revealed marked similarities. This study supports the hypothesis that many of the effects of PCC are probably due to the release of cyanide in vivo.

Animals↗
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.

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