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Biomedical subjects

R L Balster

Publications and source records attributed to R L Balster.

At least 217 records · Page 12Linked to original sources
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↗
PubMed1976

Methamphetamine self-administration in the cat.

A procedure for studing intravenous drug self-administration in the cat is described. Ten cats were given 24-h access to methamphetamine reinforcement (0.04 mg/kg/inj). The subjects maintained a significantly higher response rate for drug reinforcement than for saline. The pattern of self-administration over days alternated between periods of high and low drug intake. Six additional cats were used to study the effect of dose per injection on methamphetamine self-administration under conditions of limited access. When methamphetamine was subtituted at various doses per infusion in animals maintained on cocaine reinforcement, response rate was shown to be an inverted U-shaped function of dose. These studies demonstrate that methamphetamine is a reinforcer in the cat and its patterns of intake under conditions of 24-h and limited access resemble other species.

Animals↗
PubMed1976

Self-administration of psychomotor stimulant drugs: the effects of unlimited access.

Rhesus monkeys surgically prepared with intravenous catheters were given 23 hr daily access to injection of either cocaine, d-amphetamine, 1-amphetamine, d-methamphetamine or diethylpropion on a fixed ratio 1 schedule of reinforcement for a maximum of 30 days. Responding was maintained by all these drugs but showed both day-to-day and hour-to-hour variability. The two animals self-administering 0.2 mg/kg/infusion cocaine died in less than 5 days. All 6 animals given access to 0.05 mg/kg/infusion d-amphetamine or 0.025 mg/kg/infusion d-methamphetamine also died, but tended to survive more days than animals exposed to cocaine. Three of the 5 animals whose responding was maintained by 0.5 mg/kg/infusion diethylpropion and one of the two animals whose responding was maintained by 0.05 mg/kg/infusion 1-amphetamine survived the entire 30 days despite high rates of intake. Food intake was initially decreased, but often returned to predrug levels and was not related to level of drug intake.

Amphetamine↗
PubMed1976

Schedule-controlled behavior in the morphine-dependent rat.

The behavioral effects of acute and chronic administration of morphine and its withdrawal were studied using schedule-controlled responsing in the rat under a differential reinforcement of low rates of responding (DRL) schedule of food presentation. Acute morphine administration had a biphasic effect on response rate. Low dses (1.8-5.6 mg/kg) tended to produce a small increase and higher doses (10-30 mg/kg) decreased responding. Physical dependence was produced by twice daily injections, with an initial dose of 40 mg/kg/day which was increased by 80 mg/kg/day until reaching 600 mg/kg/day which was continued for 14 days. Throughout chronic administration the pattern of responding remained disrupted resulting in a 27-47 percent decrease in presentations of the reinforcer, while response rate was more variable and generally decreased. The effects of morphine withdrawal lasted 5 days and produced an initial maked decrease in reinforecements per hour and a biphasic change in response rate. A marked decrease in responding early in withdrawal (22.5 hr) was followed by a marked and more prolonged (70.5-118.5 hr) response rate increase.

Animals↗
PubMed1975

The effects of different atmospheric pressures of room air on the lethality of methamphetamine and pentobarbital.

Mice were used to obtain LD50's for methamphetamine and pentobarbital at 282, 380, 760, 1520, 3040, 3800 and 4560 mm Hg of room air. The animals were allowed to stabilize at the test pressure 15 min. prior to drug injections. The lethality of both methamphetamine and pentobarbital was significantly increased over sea level determinations only at 282 mm Hg. Most previous research in this area has utilized drug injections given prior to ascent or descent. The relative lack of increased toxicity under conditions of altered atmospheric pressure observed in this study compared to previous research suggests that the temporal relationship between drug administration and pressure changes is important.

Animals↗
PubMed1973

Fixed-interval schedule of cocaine reinforcement: effect of dose and infusion duration.

Rhesus monkeys were trained on a fixed-interval 9-min limited-hold 3-min schedule of intravenous cocaine reinforcement. A 15-min timeout followed each reinforcement or limited-hold expiration. An identical schedule of food reinforcement was interspersed in the session to assess rate-modifying effects of the drug infusions not specific to drug reinforcement. In one experiment, response rate for cocaine reinforcement was shown to be a positive function of reinforcement magnitude for a dose range from 0 to 800 ug/kg/inj. At these doses, there was little effect on food reinforced responding except at the highest dose, where responding decreased. Results of the second experiment indicated that increasing the duration of the cocaine infusion produced a change in response rate similar to decreasing unit dose. The response rate change for a given increase in infustion duration was less at a unit dose of 400 ug/kg than at 200 ug/kg.

Animals↗
PubMedDate not supplied

Effects of intraperitoneal carbon monoxide on fixed-ratio and screen-test performance in the mouse.

The behavioral effects of carbon monoxide (CO) administered via IP injection were investigated in the mouse. Mice were trained to lever press under a fixed-ratio (FR) 100 schedule of water reinforcement. Thirty-min test sessions were conducted either immediately or 30 min following IP injections of air (100 ml/kg) or CO (7.5, 15, 30, 50 or 100 ml/kg). CO produced a decrease in rates of responding which was exhibited earlier and lasted longer with increasing doses. Motor performance was also measured with the inverted-screen test following the same doses of CO at either 5, 15, 30, 60, 120 min or 24 hr post-injection. Performance was affected in a dose- and time-dependent fashion. Peak carboxyhemoglobin (COHb) levels were observed at 15 or 30 min and were 20%, 32%, 42%, 51% and 60% for 7.5, 15, 30, 50 and 100 ml/kg CO, respectively. COHb saturation alone was not always a good predictor of behavioral effects since both level and duration of exposure contributed to behavioral impairment. The results also show that the IP route can be used to study the toxicity of CO.

Animals↗
PubMedDate not supplied

Effects of carbon monoxide in combination with behaviorally active drugs on fixed-ratio performance in the mouse.

The effects of carbon monoxide (3.75, 7.5, 15 and 30 ml/kg, IP) alone and in combination with ethanol (1.1 g/kg), nicotine (1.1 mg/kg), caffeine (36.1 mg/kg), chlorpromazine (2.2 mg/kg), diazepam (10 mg/kg), pentobarbital (23.1 mg/kg), d-amphetamine (1.4 mg/kg) or morphine (13.3 mg/kg) were evaluated in mice. Animals were trained to lever press under a fixed-ratio 32 schedule of water reinforcement. Response rates following CO-drug combinations were compared with the expected additive effects determined by the sum of the effects of each agent administered alone. CO (15 and 30 ml/kg) in combination with ethanol produced supra-additive effects. CO-chlorpromazine and CO-d-amphetamine combinations often produced greater than additive response-rate suppression, although differences from additivity did not reach statistical significance. The effects on response rates following CO in combination with nicotine, caffeine, diazepam, pentobarbital, or morphine were additive. These results suggest that concurrent use of therapeutic or abused drugs and CO exposure may place an individual at higher risk for behavioral toxicity.

Animals↗
PubMedDate not supplied

Discriminative stimulus properties of toluene in the rat.

Rats were trained to discriminate toluene (100 mg/kg, IP) from vehicle in a two-lever operant task. Acquisition of the discrimination required a range of 85-219 training days. Injections of either methohexital (0.5-10 mg/kg) or oxazepam (0.5-20 mg/kg) produced toluene-lever responding in a dose-dependent fashion in most animals. The discriminative stimulus properties of toluene were not found to generalize to chlorpromazine (0.3-10 mg/kg). These results are consistent with those obtained in the mouse and provide further evidence that toluene has stimulus properties similar to those of CNS depressant drugs. These results further suggest that toluene may have drug abuse potential of the CNS depressant type.

Animals↗
PubMedDate not supplied

Effects of inhaled 1,1,1-trichloroethane on locomotor activity in mice.

To quantify the motoric effects of an abused solvent, photocells were added to two exposure systems. The first system utilized a static exposure chamber that recirculated vapor-laden air. A second dynamic system allowed for removal of waste gases with replenishment of fresh air combined with test vapors. In the present studies, male mice were examined for effects on locomotor activity following 30-min inhalation exposures to several concentrations of 1,1,1-trichloroethane (TCE), a widely used and abused solvent. TCE produced significant increases in locomotor activity at intermediate concentrations. Minimally effective concentrations for activity-increasing effects in the dynamic and static systems were 1,250 ppm and 2,500 ppm, respectively. At higher concentrations, motor activity was decreased with the highest dynamic system concentration (10,000 ppm), resulting in 26% of baseline control values. Biphasic, motor activity increasing and decreasing effects of TCE as a function of exposure concentration may reflect the CNS-depressant drug-like effects of abused solvents.

Administration, Inhalation↗
PubMedDate not supplied

Functional observational battery comparing effects of ethanol, 1,1,1-trichloroethane, ether, and flurothyl.

Several recent reports have demonstrated that acute solvent exposure in animals produces a profile of neurobehavioral effects similar to that of classical CNS depressant drugs such as the barbiturates and ethanol. The present investigation further delineated the behavioral pharmacology of three solvents [1,1,1-trichloroethane (TCE), ether, and flurothyl] using a functional observational battery (FOB) composed of 21 qualitative and quantitative measures of behavior. The profiles of acute effects produced by TCE and ether were similar to one another and similar to the profile of effects produced by the IP administration of ethanol. This profile of depressant effects included changes in posture, decreased arousal, disturbances in gait, decreased forelimb grip strength, increased landing foot splay, and impaired psychomotor coordination. Flurothyl exposure also produced dose-related effects on many of the measures in the FOB; however, unlike the depressant vapors, flurothyl did not affect measures of muscle tone and equilibrium such as forelimb grip strength and landing foot splay, or measures of sensorimotor reactivity, including the touch response and tail pinch response. In addition, flurothyl produced handling-induced convulsions in some mice. Recovery from the acute effects of these vapors was rapid and began within minutes of removal from the exposure chamber. These results provide further evidence that exposure to certain solvents produces a profile of reversible effects qualitatively similar to that produced by depressant drugs and alcohol, and that the FOB can be used to compare and contrast profiles of depressant and excitatory effects of inhalants.

Animals↗