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Biomedical subjects

R L Balster

Publications and source records attributed to R L Balster.

At least 145 records · Page 8Linked to original sources
PubMed1985

Anticonvulsant properties of phencyclidine-like drugs in mice.

Primarily on the basis of activity in [3H]phencyclidine (PCP) binding assays and drug discrimination studies, a number of structurally dissimilar compounds have been found to be PCP-like. Drugs from four of these classes of PCP-like compounds were examined for anticonvulsant activity in the pentylenetetrazol (PTZ) seizure test. Male albino mice, eight per dose, were administered the drug or vehicle i.p. 10 min before PTZ (125 mg/kg s.c.). At each dose, the number of subjects and latency to clonic and/or tonic seizures within 15 min following PTZ were recorded. The anticonvulsant properties of PCP, ketamine, (+)-N-allylnormetazocine, etoxadrol, dexoxadrol and (-)-2-methyl-3,3-diphenyl-3-propanolamine ((-)-2-MDP) were selective for tonic seizures. The highest dose tested for each compound completely prevented the occurrence of tonic seizures. Levoxadrol and (+)-2-MDP, drugs devoid of PCP-like activity in other tests, were also inactive in the PTZ seizure test. These results demonstrate that similarities among PCP-like drugs previously shown using binding assays and drug discrimination procedures can be extended to include anticonvulsant effects, and they suggest common cellular sites of action for these properties.

Animals↗
PubMed1985

Inhaled toluene produces pentobarbital-like discriminative stimulus effects in mice.

The abuse of volatile solvents may be due to their ability to produce an intoxication similar to that produced by classical central nervous system depressants such as the barbiturates and ethanol. To evaluate this hypothesis, mice were trained to discriminate pentobarbital from saline injections in a two-lever operant task. Stimulus generalization was examined following 20-min inhalation exposures to toluene (300-5400 ppm). In 8 of 10 subjects, pentobarbital-lever responding occurred following toluene exposure indicating an overlap in the discriminative stimulus properties of toluene and pentobarbital.

Aerosols↗
PubMed1985

Effects of xylene isomers on operant responding and motor performance in mice.

Xylene, a widely used industrial solvent, is a mixture of the ortho-, meta-, and paraisomers. In this study we examined the effects of each individual isomer, as well as a commercial-grade mixture of xylenes, on two behavioral measures: (1) operant performance of 15 mice trained to lever-press under a DRL (differential reinforcement of low rates) 10-sec schedule, and (2) motor performance of mice on an inverted screen test. The 15-min operant sessions immediately followed 30-min exposures to solvent vapors (500 to 7000 ppm), or air, in static inhalation chambers. All mice were exposed to each isomer in a counterbalanced order, and the mixture was given last in all cases. Ortho-, meta-, para-, and mixed xylenes produced similar biphasic effects on response rates, and concentration-dependent decreases in reinforcement rates. The lowest significantly effective concentration for each isomer on any variable was 1400 ppm, where increases in response rates occurred. Half-maximal response rate decreases were produced by 5179 ppm (ortho-xylene) to 6176 ppm (meta-xylene). The temporal distribution of responses was only moderately disrupted, even at high concentrations. In other groups of mice, motor coordination was also disrupted by the xylenes in a concentration-dependent manner. Half-maximal effective concentrations were 2676 ppm (para-xylene) to 3790 ppm (meta-xylene). Minimally effective concentrations were 2000 to 3000 ppm, higher than those seen in the operant studies. Xylene produced pronounced behavioral actions following acute exposure and no substantial differences in overall effects, and only slight potency differences, were obtained between the individual isomers or the commercial mixture.

Animals↗
PubMed1985

A comparison of the discriminative stimulus properties of phencyclidine, given intraperitoneally or intraventricularly in rats.

Rats trained to discriminate intraperitoneally injected phencyclidine (PCP) from saline in a two-lever operant procedure distributed most of their responses on the phencyclidine lever after administration of 150 or 300 micrograms of phencyclidine into a lateral ventricle. This demonstrated that the discriminative stimulus properties of phencyclidine were centrally mediated. On the other hand, the potency of phencyclidine was increased by no more than about 7-fold from intraperitoneal to intraventricular administration. This suggests that either periventricular sites are not involved in mediating the discriminative stimulus properties of phencyclidine or that absorption of phencyclidine to relevant sites in the brain is not markedly enhanced by intraventricular administration.

Animals↗
PubMed1985

Acute motor and lethal effects of inhaled toluene, 1,1,1-trichloroethane, halothane, and ethanol in mice: effects of exposure duration.

Some acute effects of inhalation exposure to toluene, 1,1,1-trichloroethane (1,1,1-TCE), halothane, and ethanol were examined in mice. Lethality and performance on an inverted screen test of motor performance were measured following 10-, 30-, and 60-min exposures. Concentration-dependent effects were obtained on both measures for all solvents except that lethal concentrations of ethanol could not be produced under these exposure conditions. Lethality increased with longer exposures for toluene, 1,1,1-TCE, and halothane. Sensitivity to the motor effects of 1,1,1-TCE, halothane, and ethanol increased when exposure duration was increased from 10 to 30 min, with no further change with 60-min exposures. In contrast, behavioral sensitivity to toluene increased over the entire range of exposure durations. The relative lipid solubilities of the solvents correlate with potency for behavioral activity but not as well with potency for lethality. The ratio of potency for motor and lethal effects depended on the chemical studied and in some cases exposure duration. These results demonstrate that both concentration and exposure duration determine the effects of inhaled compounds, but a simple linear relationship does not exist and it depends upon the effect measured.

Animals↗
PubMed1985

The effects of acute and repeated clonidine administration on fixed-interval performance in rhesus monkeys.

The effects of clonidine before, during and after 95 days of chronic administration of 100 micrograms/kg/day clonidine were investigated in five rhesus monkeys which had been trained to lever press under a fixed interval 5-min schedule of food presentation. The effects of clonidine (3-100 micrograms/kg) were generally to cause dose-related decreases in rates of responding and quarter-life, and increases in the line slopes of rate-dependency plots. Before chronic treatment, 200 micrograms/kg of clonidine caused somewhat less response rate suppression than 100 micrograms/kg. During chronic treatment, one monkey showed some development of tolerance to the rate-suppressant effects and another showed tolerance to the quarter-life effects, but the group as a whole did not show evidence of tolerance development to these effects of clonidine. Following cessation of chronic treatment, no overt signs of dependence were observed, however, some subjects did show disruption of schedule-controlled performance during the first week. In general, however, no consistent evidence for the development of tolerance or dependence to clonidine were observed under these dosing conditions.

Animals↗
PubMed1985

Discriminative stimulus properties and brain distribution of phencyclidine in rats following administration by injection and smoke inhalation.

Four male Sprague-Dawley rats were trained to discriminate IP injections of 3.0 mg/kg phencyclidine (PCP) from saline under a 2-lever fixed-ratio 32 schedule of food presentation. After reliable discriminative control of lever choice was established, other doses of injected PCP were tested resulting in dose-dependent increases in PCP-lever selection and dose-dependent decreases in rates of responding. When doses of PCP were administered by exposure to smoke from cigarettes containing PCP, a dose-dependent increase in PCP-lever responding was also observed. delta 9-Tetrahydrocannabinol administered via smoke exposure, up to doses which markedly suppressed response rates, did not result in PCP-appropriate responding, demonstrating the specificity of the PCP stimulus by the inhalation route. Brain levels and distribution of 3H-PCP were determined in rats administered doses calculated to result in 50% generalization by the IP injection or smoke inhalation routes. By both routes of administration roughly equivalent brain levels were attained and the distribution was relatively even across the seven brain areas analyzed. These results demonstrate the validity of using the injection route of administration when studying PCP experimentally, in spite of the fact that PCP is abused primarily by smoking.

Animals↗
PubMed1985

Intravenous self-administration of nicotine: with and without schedule-induction.

In Experiment I, rhesus monkeys were trained to lever press on a concurrent fixed-interval 5-min (food pellets) fixed-ratio 1 (IV nicotine-injection) schedule of reinforcement. All three monkeys self-administered nicotine (0.1-100 micrograms/kg/injection) at two or more doses during the concurrent conditions (Concurrent I or II) at rates that exceeded saline control or rates of nicotine-maintained responding on a simple fixed-ratio 1 schedule (No Food condition). At least one dose of nicotine did maintain FR 1 responding which was greater than saline rates on the single component schedule and these rates were not increased by the addition of a concurrent schedule of food reinforcement. During the concurrent schedule, nicotine-maintained responding occurred throughout the 60-min session in contrast to the No Food (FR 1) condition where most injections of nicotine were self-administered during the initial segments of the session. In general, nicotine injections occurred during the early portions of the interval, although this varied between individual animals. In Experiment II, rhesus monkeys were trained to lever press for intravenous injections of cocaine (50 micrograms/kg/injection) on a fixed-ratio 10 schedule of reinforcement. During testing, doses of nicotine (1-300 micrograms/kg/injection) or saline were substituted for cocaine. Nicotine maintained FR 10 responding at rates that exceeded saline self-administration at one or more doses in all four monkeys. These doses were similar to those that functioned as positive reinforcers in Experiment I. These two experiments demonstrate that nicotine can function as a positive reinforcer to maintain FR 1 or FR 10 responding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of toluene, halothane and ethanol vapor on fixed-ratio performance in mice.

The behavioral effects of inhalation of the vapors of volatile compounds representative of different chemical groups were studied in mice under conditions where behavior and exposure concentrations could be concurrently monitored. The magnitude and time course of the effects of toluene, halothane and ethanol inhalation on fixed-ratio (FR) responding were compared. The subjects were trained to lever-press under a FR-100 schedule of water reinforcement. Daily operant sessions took place in the exposure chambers, and solvent exposures were conducted once a week. The test exposures lasted for 20 min, and the sessions continued until the subjects resumed baseline rates of responding to give a measure of recovery. All solvents produced concentration-dependent response rate decreases, and only halothane showed any evidence of response rate increases at low concentrations. Halothane quickly produced maximal response rate-decreasing effects and recovery was rapid, while the effects of toluene became progressively greater during the exposure and recovery was prolonged. Ethanol displayed the most rapid onset and recovery of effects. Thus, these solvents produced somewhat similar effects on FR responding but displayed potency and time course differences.

Animals↗
PubMed1985

Attenuation of cyclophosphamide-induced taste aversions in mice by prochlorperazine, delta 9-tetrahydrocannabinol, nabilone and levonantradol.

A series of experiments were performed with adult CD-1 male mice to evaluate the antiemetic effects of several compounds using the conditioned taste aversion procedure. The antiemetics were administered IP immediately prior to a 30-min conditioning trial in which a novel tasting solution (0.3% saccharin) was presented to the subjects. The emetics, apomorphine and the cancer chemotherapeutic drug cyclophosphamide, were given IP immediately after the conditioning trial at doses that induced taste aversions. Three days later the mice received a two bottle preference test (saccharin vs. water) and the percent saccharin consumed of the total fluid intake was calculated. Doses of the phenothiazine antiemetic prochlorperazine (1 and 3 mg/kg) attenuated the aversions produced by 0.3 and 1.0 mg/kg apomorphine. Doses of drugs currently approved or under clinical investigation as antiemetics in conjunction with cancer chemotherapy, i.e., prochlorperazine (1.0 mg/kg), delta 9-tetrahydrocannabinol (0.3 and 1.0 mg/kg) and nabilone (0.01 and 0.03 mg/kg), significantly attenuated the taste aversions induced by cyclophosphamide. Levonantradol at doses of 0.03 and 0.06 mg/kg, however, did not attenuate cyclophosphamide-induced taste aversions. Conditioned taste aversions produced by emetic drugs warrants investigation as a model for evaluating potential antiemetics.

Animals↗
PubMed1985

Review of self-administration.

The reinforcing properties of drugs can be evaluated pre-clinically using self-administration procedures in laboratory animals. This paper reviews self-administration studies of the four opioid agonist/antagonist analgesics pentazocine, butorphanol, nalbuphine and buprenorphine, and compares these results to those from studies of morphine and cyclazocine. All four agonist/antagonists possess reinforcing properties under at least some test conditions. In this respect they more resemble morphine than cyclazocine. These results suggest that they all may have some potential for recreational use. On the other hand, some data point to a lower reinforcing efficacy for these agonist/antagonists than for the pure agonists such as morphine. Studies comparing the reinforcing efficacy among the agonist/antagonists are also reviewed, however more data are needed before definitive conclusions can be drawn within the class.

Animals↗
PubMed1985

Minimal tolerance to the effects of 1,1,1-trichloroethane on fixed-ratio responding in mice.

Most laboratory animal studies of the behavioral or neurophysiological effects of repeated exposures to volatile organic solvents find little evidence for substantial tolerance. This study examined the development of tolerance to the effects of 1,1,1-trichloroethane (1,1,1-TCE) on fixed-ratio responding in four mice. The subjects were exposed to 6000 ppm solvent vapor for 20 min of the daily 45-min operant sessions. Once a week, a series of four concentrations (1000-8000 ppm) were substituted for the daily exposure in order to obtain a cumulative concentration-effect curve. This proved to be a rapid and reliable method with which to ascertain the effects of 1,1,1-TCE over a range of concentrations. During the 15 days of 20-min exposure, the subjects showed a slight but significant increase in both response rates during exposure and in the rate of recovery following exposure. Maximal changes in these measures were evident in the first 7 days, with no further decreased sensitivity over the final 8 days of exposure. The concentration-effect curves determined during and after the daily exposures showed no significant shifts in either direction from the initial curve. Thus, while some alteration in the daily acute effects was noted, this tolerance was not of large magnitude and could not be detected as a change in the concentration-effect curve.

Air Pollutants↗
PubMed1984

Behavioral and biochemical stereoselectivity of sigma opiate/PCP receptors.

The relative potencies of the stereoisomers of ketamine, N-allylnormetazocine and cyclazocine were determined at mu opiate and sigma opiate/phencyclidine (PCP) receptors in vitro in rat brain homogenates, as well as in a discriminative stimulus behavioral paradigm in rats trained to discriminate PCP from saline. In all cases the in vivo and in vitro data were in agreement. The (+)-isomers of N-allylnormetazocine and cyclazocine are highly specific sigma opiate/PCP ligands.

Animals↗
PubMed1984

Relationship between the development of behavioral tolerance and the biodisposition of phencyclidine in mice.

Mice trained on a differential reinforcement of low rate 10-sec schedule (DRL 10) were treated daily with either IP saline or 10 mg/kg of phencyclidine hydrochloride (PCP). After 21 consecutive days of treatment, dose-effect determinations for PCP were obtained in both groups. Chronic treatment with PCP resulted in approximately 1.5-fold development of tolerance to the PCP-induced reduction of reinforcement rate. Following completion of the dose-effect determinations, the mice were treated for an additional 13 days with either saline or PCP (10 mg/kg, IP). On the fourteenth day, the biodisposition of 3H-PCP-HCl (10 mg/kg, IP) was studied in both groups. The ratio of the brain levels of PCP in the saline-trained animals to that in the PCP-trained animals was 1.3 to 1 which accounted in large part for the development of tolerance. It appears that dispositional factors are involved in the development of tolerance of mice to the disruptive effects of PCP on DRL performance.

Animals↗
PubMed1984

Behavioral dependence produced by continuous phencyclidine infusion in rhesus monkeys.

The effects of continuous i.v. phencyclidine (PCP) infusion and withdrawal on operant behavior were studied in rhesus monkeys. The monkeys were trained to lever press under a fixed-ratio 100 schedule of food presentation. They responded under this schedule during four daily 30-min periods conducted every 6 hr. After at least 5 days of continuous saline infusion through indwelling i.v. catheters, the subjects received 10 days of continuous infusion of 0.05 mg/kg/hr of PCP. During chronic PCP, rates of responding increased above saline control values. When saline was substituted for PCP, responding was suppressed markedly. This suppression of responding occurred within 8 hr of saline substitution and lasted several days. Mild signs of withdrawal were seen within 3 hr after saline substitution and dissipated by 48 hr. These signs included muscle tremors, oculomotor hyperactivity and increased aggressiveness. After responding during saline infusion had returned to control levels, continuous PCP infusion was resumed. Withdrawal effects on behavior decreased in intensity after repeated withdrawals and it was necessary to raise the infusion dose to produce consistent withdrawal disruption of behavior. Withdrawal-induced disruption in responding was reversed by acute pretreatment with PCP (0.01-0.3 mg/kg i.m.) in a dose-related fashion. Presession administration of naloxone (0.1-1.0 mg/kg i.m.) during chronic PCP infusion failed to precipitate withdrawal signs or disrupt operant responding, suggesting that PCP dependence is not of the opioid type. The results of this study indicate that operant behavior is disrupted during withdrawal from chronic PCP and can be used as evidence of behavioral dependence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Some effects of the formamidine pesticide chlordimeform on the behavior of mice.

Three experiments were performed to determine the behavioral effects of acutely administered chlordimeform (1-56 mg/kg, i.p.) to male mice. In Experiment I, dosages of 30 and 56 mg/kg decreased the amount of time spent investigating a female conspecific. In Experiment II, large dosages of chlordimeform (30 and 56 mg/kg) decreased vertically directed activity (rearing) to a proportionately greater extent than horizontally directed activity (ambulation). In Experiment III, chlordimeform produced conditioned flavor aversions that were intermediate at 10 mg/kg and maximal at 30 mg/kg. In an additional experiment (Experiment IV), the LD50 for chlordimeform was determined to be 95.6 mg/kg. Behavioral effects were thus obtained at dosages that were approximately 10 to 30% of the LD50.

Amidines↗