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Biomedical subjects

R L Balster

Publications and source records attributed to R L Balster.

At least 163 records · Page 9Linked to original sources
PubMed1983

Discriminative stimulus properties of buspirone compared to central nervous system depressants in rats.

Two groups of rats were trained to discriminate either IP buspirone from vehicle or IP oxazepam from vehicle using a two-lever FR-10 schedule of sweetened milk presentation. The discrimination in the buspirone group was difficult to establish due to potent response rate decreasing effects. Oxazepam was a very effective stimulus and the discrimination in the oxazepam group was readily established. Tests with oxazepam and pentobarbital in the buspirone group provided no evidence for generalization of the stimulus properties of buspirone to either drug. Tests with buspirone in the oxazepam group also provided no evidence of generalization to buspirone, although tests with pentobarbital indicated almost complete generalization. Finally buspirone and oxazepam were tested in a group of rats previously trained to discriminate pentobarbital from vehicle. The findings supported the data obtained in the buspirone and oxazepam groups, with no indication of generalization from pentobarbital to buspirone, but with complete generalization to oxazepam. These data suggest that buspirone does not share discriminative stimulus properties which are common to other CNS depressants.

Animals↗
PubMed1983

Effects of local anesthetics on fixed-interval responding in rhesus monkeys.

Several local anesthetics of both the ester and amide type were administered IM to rhesus monkeys trained to respond on a fixed-interval 5 min schedule of food delivery. With the exception of procainamide, all local anesthetics produced dose-related decreases in response rates. Effects on pattern of responding varied between local anesthetics. With some (cocaine, dimethocaine and lidocaine), rate-dependent effects were apparent. When control rates were low, these compounds increased rates; when control rates were high, they decreased rates. However, with others (procaine, chloroprocaine, tetracaine and propoxycaine) no rate-dependent effects were noted; i.e., these compounds had little or no effect on the pattern of responding, even at doses that substantially reduced response rates. Consistent with other experiments with these compounds, cocaine was the most potent of the group. In several instances, local anesthetics which had similar stimulus properties in other behavioral paradigms differed in terms of their effects on fixed-interval behavior.

Anesthetics, Local↗
PubMed1983

Reinforcing properties of stereoisomers of the putative sigma agonists N-allylnormetazocine and cyclazocine in rhesus monkeys.

There are many similarities in the effects of phencyclidine (PCP) and opioids with sigma agonist activity such as N-allylnormetazocine (SKF-10,047) and cyclazocine. Yet PCP and sigma agonists differ in reinforcing properties. PCP is reliably self-administered in animal models and has abuse liability in humans, whereas (+/-)-N-allylnormetazocine and (+/-)-cyclazocine are not self-administered or abused. Inasmuch as other research has demonstrated differences in the selectivity of PCP-like effects of the stereoisomers of opioids, this study compared the reinforcing properties of PCP to the reinforcing properties of isomers of N-allylnormetazocine and cyclazocine. Rhesus monkeys were trained to lever-press on a fixed-ratio 10 schedule for i.v. cocaine (50 micrograms/kg/injection). During substitution tests, cocaine was replaced with various doses of test drugs or vehicle. The drugs tested were PCP, (+/-)-N-allylnormetazocine, (-)-N-allylnormetazocine, (+)-N-allylnormetazocine, (+/-)-cyclazocine, (-)-cyclazocine and (+)-cyclazocine. PCP and the (+)-isomers of both benzomorphans, at one or more doses, were self-administered at rates which exceeded rates maintained by vehicle and which equaled or exceeded cocaine-maintained base-line rates. Neither the racemates nor the (-)-isomers of N-allylnormetazocine or cyclazocine were self-administered by the monkeys at rates which were greater than vehicle control levels of responding. Reinforcing doses of the three compounds resulted in injections evenly distributed across the 60-min session in a pattern similar to cocaine self-administration, whereas the racemic mixtures and the (-)-isomers produced negatively accelerated patterns of injections which resembled typical saline patterns of extinction responding. These data provide further evidence that the (+)-isomers of sigma agonists are more selective for PCP-like effects than the (-)-isomers in monkeys.

Animals↗
PubMed1982

Discriminative stimulus properties of stereoisomers of cyclazocine in phencyclidine-trained squirrel monkeys.

Squirrel monkeys were trained to discriminate 0.16 mg/kg phencyclidine (PCP) from saline in a two-layer drug discrimination task on a fixed-ratio 32 schedule of food presentation. After reliable discriminative control of lever choice was established, dose-response determinations for generalization to the training dose of PCP were made with several doses of PCP, a racemic mixture of cyclazocine and the pure (+)- and (-)-isomers of cyclazocine. Only PCP and the (+)-isomer produced dose-dependent PCP-appropriate responding. Neither the racemic mixture nor (-)-cyclazocine produced over 25% PCP-appropriate responding at any of the doses tested. (+)-Cyclazocine was eight times less potent than PCP in producing drug-lever appropriate responding. (-)-Cyclazocine was about 30 times more potent than PCP and over 200 times more potent than (+)-cyclazocine in overall response rate suppression. The potency of the racemic mixture for response-rate suppression was consistent with an additive effect of the isomers. Neither the PCP-lever appropriate responding produced by (+)-cyclazocine nor the response-rate suppression produced by (-)-cyclazocine were antagonized by naloxone. Thus, racemic cyclazocine is composed of two isomers with differing behavioral effects. The (-)-isomer is more potent, and the (+)-isomer has more specificity for PCP-like effects.

Animals↗
PubMed1982

Stereoisomers of N-allylnormetazocine: phencyclidine-like behavioral effects in squirrel monkeys and rats.

(+/-)-N-Allylnormetazocine is a benzomorphan opioid with psychotomimetic effects. The pure stereoisomers of this compound, as well as the racemic mixture, were compared to phencyclidine for their behavioral effects on squirrel monkeys and rats trained to discriminate phencyclidine from saline. Dose-response determinations were made for responses to phencyclidine, to a racemic mixture of N-allylnormetazocine, and to the pure levo and dextro isomers of N-allylnormetazocine. In both rats and monkeys, the dextro isomer and the racemic mixture produced dose-dependent responses appropriate for phencyclidine; the levo isomer did not produce the responses appropriate for phencyclidine at any of the doses tested. In both species, the levo isomer was more potent than the dextro isomer in decreasing the rate of responding. Thus racemic N-allylnormetazocine is a mixture of compounds that produce different behavioral effects.

Animals↗
PubMed1982

A new test for social investigation in mice: effects of d-amphetamine.

A new automated device that concurrently records social investigatory responses and spontaneous motor activity is described and the effects of d-amphetamine are presented. The rectangular Plexiglas apparatus was divided into three compartments, separated from each other by wire mesh screens. A male mouse was placed into the center compartment and the amount of time spent investigating the two adjacent stimulus compartments was recorded using contact circuits. One stimulus compartment housed a female conspecific, while the other remained uninhabited and served as a control for nonsocial investigatory responses. A photo-cell bisected the center compartment and recorded motor activity. Doses of 0, 0.3, 1.0, and 3.0 mg/kg d-amphetamine administered to both sexually naive and sexually experienced male mice resulted in a dose-dependent decrease in investigation of both stimulus chambers, however social investigation was significantly affected at a lower dose. Both groups of males preferred the female to the uninhabited chamber at all but the highest dose of d-amphetamine, which abolished the preference. Locomotor activity for both inexperienced and experienced males increased with increasing doses of d-amphetamine.

Animals↗
PubMed1982

Reinforcing properties of clonidine in rhesus monkeys.

Intravenous clonidine self-administration was studied in rhesus monkeys under conditions of limited and unlimited access. Limited access consisted of daily 2-h experimental sessions with drug available on a fixed ratio 10 schedule. For unlimited access, drug was available 23 h/day with each response resulting in an injection. In all animals under both conditions, responding was maintained at levels that were above those maintained by saline injections at doses between 0.3 and 10 microgram/kg/inj, and the number of injections taken per session depended upon the dose. Under conditions of limited access, peak self-administration rates varied between animals but averaged approximately 30 inj/session. Total session intake was occasionally in excess of 1.0 mg/kg. Under conditions of unlimited access animals frequently self-administered more than 300 inj/day and intakes averaging 3.6 mg/kg/day occurred at the highest dose tested (10 microgram/kg/inj). When saline was substituted for clonidine after periods of clonidine access that ranged from 10-40 days, withdrawal signs included facial flushing, refusal of preferred food, restlessness, salivation, and emesis. These signs could be reversed with IV clonidine but could not be reliably precipitated with IV naloxone.

Animals↗
PubMed1982

Discriminative stimulus properties of ketamine stereoisomers in phencyclidine-trained rats.

Rats were trained to discriminate phencyclidine (PCP) from saline in a two-lever drug discrimination task on a fixed-ratio 32 schedule of food presentation. The subjects were given IP injections of 3.0 mg/kg PCP or saline daily on a double alternation schedule. After reliable discriminative control of lever choice was established, dose-response determinations for generalization to the training dose of PCP were made with several doses of PCP, a racemic mixture of ketamine and the pure levo (-) and dextro (+) salts of ketamine. All three forms of ketamine produced dose-dependent PCP-appropriate responding. ED50 values were determined for each drug for percent drug-lever appropriate responding and for suppression of operant responding during test sessions. There was a greater difference between doses which produced drug-lever appropriate responding and doses which suppressed response rates for PCP than for any of the forms of ketamine. (+/-)- and (+)-ketamine were about 2 times more potent than (-)-ketamine for producing drug-lever appropriate responding but were roughly equipotent for response rate suppression. Thus there is no qualitative and little quantitative stereospecificity for the PCP-like discriminative stimulus effects of ketamine in rats.

Animals↗
PubMed1982

Opiate effects on social investigatory behavior of male mice.

The effects of morphine and naloxone, alone and in combination, on social investigatory behavior and motor activity was examined in CD-1 male mice. Tests were conducted in a Plexiglas apparatus in which a center area was separated from two adjacent stimulus compartments by wire mesh screens. One compartment housed a female conspecific while the other remained empty and served as a control for non-specific investigatory responses. A photocell bisected the center compartment and recorded motor activity. Male mice were placed individually into the center area and the time spent investigating each screen was recorded using contact circuits during the 15-min test. In Experiment 1, males (N = 11) received saline, 0.1, 1.0 and 10.0 mg/kg morphine sulfate IP 20 min prior to testing. The high dose significantly decreased investigation of the female compartment while investigation of the uninhibited chamber and motor activity were not significantly affected. In a second experiment (N = 16), 3, 10 and 30 mg/kg naloxone administered 30 min prior to testing had no significant effect on any of the measures recorded. In a third group of subjects (N = 16), 3 mg/kg naloxone reversed the decrease in female investigation time observed with 10 mg/kg morphine, indicating an opiate mechanism for these results. These data provide further evidence that an animal model can be used to study the disruption of socio-sexual behavior produced by opiates.

Animals↗
PubMed1982

Concurrent measurement of solvent vapor concentrations and effects on operant behavior using a dynamic exposure system.

A method is described for exposing mice, lever-pressing on an operant schedule for water reinforcement, to continuously-generated solvent vapors. Concurrent monitoring of chamber concentration and schedule-controlled behavior allows a correlation of the magnitude and time course for behavioral effects with changes in the levels of solvent exposure. Data are presented showing the acute effects of 1,1,1-trichloroethane over the range of 1000-8000 ppm on behavior maintained by a fixed-ratio 100 schedule of water presentation. Concentration-dependent decreases in response rates with a rapid onset and recovery were obtained.

Animals↗
PubMed1982

The effects of aggregation on the lethality of phencyclidine in mice.

The lethal effects of d-amphetamine and phencyclidine (PCP) were compared when adult male mice were placed into isolated or aggregated (12 mice/cage) conditions. The LD50 of d-amphetamine decreased approx. 30-fold between isolated (87.9 mg/kg) and aggregated (2.8 mg/kg) conditions. In contrast, PCP showed only a 1.3-fold increase in toxicity between isolated (64.5 mg/kg) and aggregated (48.4 mg/kg) conditions. These results suggest different mechanisms for the acute lethal effects of d-amphetamine and PCP in mice.

Animals↗
PubMed1982

Behavioral toxicity of trihalomethane contaminants of drinking water in mice.

The behavioral toxicity of trichloromethane (TCM), dichlorobromomethane (DCBM), dibromochloromethane (DBCM) and tribromomethane (TBM) was evaluated following oral administration in mice. A variety of dosage regimens and behavioral measures were used. Studies included acute dose effect, 14-and 90-day treatments at 300 and 3000 times the estimated average human daily intake of contaminated drinking water, 30 days of 100 mg/kg/day, and 60 days of 100 and 400 mg/kg/day. In addition, TCM was tested for the production of taste aversions with 10-day administration and for behavioral teratology in offspring following extensive perinatal exposure. The ED50 for acute effects on a screen test of motor performance was about 500 mg/kg for all four trihalomethanes. The 14-day treatments had no effect on swimming behavior and the 90-day treatments had no effect on bar clinging, a test of motor coordination, and a measure of exploratory behavior. None of the compounds produced effects on passive-avoidance learning following 100 mg/kg/day for 30 days. TCM, DBCM and TBM elicited clear effects at both 100 and 400 mg/kg/day on operant behavior when administered for 60 days. DBCM elicited clear effects at 400 mg/kg/day. These effects on operant behavior were seen following the first dose and tolerance tended to develop. Thus, there was no evidence from these studies for a progressive neurotoxicity from trihalomethanes in adult mice. A behavioral teratology study was also conducted with TCM. Both parents were treated with 31.1 mg/kg/day TCM, and treatment of the dam continued throughout gestation and lactation. No clear evidence for behavioral effects in the offspring were observed. The most sensitive measure for the effects of TCM was the taste aversion paradigm in which saccharin aversions were produced after a single treatment of 30 mg/kg.

Administration, Oral↗
PubMed1982

Intravenous buspirone self-administration in rhesus monkeys.

Rhesus monkeys trained to press levers for intravenous cocaine injections were tested with saline and various doses of buspirone, chlordiazepoxide, and clorazepate. Buspirone was not self-administered at rates significantly above saline control levels. Chlordiazepoxide and clorazepate also failed to serve as reinforcers under these conditions. The lack of reinforcing properties, taken together with the results of other preclinical behavioral studies, suggests a low potential for recreational use of buspirone in man.

Animals↗