Four juvenile male baboons were trained on a delayed match-to-sample (MTS) discrimination task. Single administration of 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 mg/kg diazepam (DZ) resulted in a dose-related increase in mean response time (MRT), with a maximum effect at 2.0 mg/kg. Administration of 0.25 mg/kg of DZ had no effect. Response time was increased significantly by 1.0 g/kg of ethanol (EtOH) but was not affected by 0.5 g/kg EtOH. There were no significant effects on the number of correct responses. Combined treatment of 0.5 g/kg of EtOH with 1.0 mg/kg DZ produced the same increase in MRT as the DZ alone. When 1.0 g/kg EtOH was administered with 0.25 mg/kg DZ. MRT decreased which was a significant improvement in performance as compared to the increase in MRT observed with either the EtOH or the DZ alone. Combined doses of 1.0 g/kg EtOH and 0.5 mg/kg DZ produced essentially the same increases in MRT as either dose alone. Similar results were obtained when 1.0 g/kg EtOH and 1.0 mg/kg DZ were combined and the increase in MRT was about the same for DZ alone and more than twice as great for the EtOH alone. Combined administration of the drugs had no significant effects on the number of correct choices. Since the administration of a combination of a low dose of DZ with EtOH appeared to prevent the increases in MRT observed with either drug alone and there were no observable effects on the number of correct response, these effects do not appear to involve cognitive processes but might be related to excitability changes in motor systems.

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Behavioral effects of drugs as a function of maternal polybrominated biphenyl body burden.

Prior to breeding, female rats were dosed orally for 20 days with either 0.5 mg/kg polybrominated biphenyl (PBB), 5.0 mg/kg PBB, or the lecithin liposome vehicle. Male offspring of these 3 treatment groups did not differ with respect to the learning of an operant discrimination task. However, administration of phenobarbital or d-amphetamine impaired the behavior of the offspring of low-dose PBB dams less than that of the offspring of controls. The behavioral effects of the drugs were generally inversely related to levels of liver PBB and activities of liver aryl hydrocarbon hydroxylase (AHH).

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PubMedDate not supplied

Ethanol and diazepam interactions on conflict behavior in rats.

Twenty-four adult male rats trained on the Geller-Seifter conflict procedure received: 1.0, 2.0, or 4.0 mg/kg diazepam at 15 min, 0.25, 0.5, 1.0, 2.0, or 4.0 g/kg of ethanol (EtOH) at 30 min prior to the test session, or combinations of the same diazepam doses and 0.5 g/kg of EtOH. Ethanol administration produced a significant (p less than 0.05) dose-related decrease in lever pressing during the periods prior to the introduction of the tone stimulus, compared to lever pressing during the corresponding control periods on the day prior to drug treatment. During the posttone periods 0.25 g/kg increased lever pressing (p less than 0.05), while doses of EtOH from 0.5 to 4.0 g/kg resulted in significantly lower levels of lever pressing in periods following the discontinuation of the tone. In the presence of the conflict evoking tone stimulus, rats treated with 2.0 g/kg of EtOH increased their rate of lever pressing, while animals receiving the other EtOH doses exhibited lever pressing comparable to that observed during the corresponding control periods. Administration of EtOH had no effect on the number of reinforcements received during the entire test session, except for a significant (p less than 0.05) reduction at the highest dose of 4.0 g/kg. Diazepam increased the number of reinforcements received during the entire test session as compared to those obtained during control sessions. Lever pressing was not affected by diazepam treatment during pretone or tone periods. During the posttone periods responses were significantly (p less than 0.05) increased in rats receiving the lowest dose of 1.0 mg/kg of diazepam but the other doses were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMedDate not supplied

Interactive effects of diazepam and ethanol on baboon match-to-sample performance.

Four juvenile male baboons were trained to perform a match-to-sample (MTS) discrimination task. Diazepam (DZ) at doses of 0.5, 1.0, 2.0, 4.0, or 6.0 mg/kg resulted in a significant (p less than 0.05) increase in the mean response times (MRT) during the 2 hr test session in terms of percent change from baseline performance under nondrug conditions measured the day prior to drug treatment. Effects were maximal at 2.0 mg/kg diazepam and no further effects were observed at 4.0 or 6.0 mg/kg. Administration of 0.25 mg/kg of diazepam had no effect on MTS performance. Exposure to 0.5 g/kg of ethanol (EtOH) had no effect on response time, while 1.0 g/kg EtOH significantly (p less than 0.05) increased response time. Baboons receiving combined treatment with 0.5 or 1.0 g/kg EtOH plus 1.0 mg/kg diazepam displayed a significant (p less than 0.05) percent increase in mean response time compared to that observed under baseline conditions on the day prior to drug treatment. The 0.5 g/kg EtOH and 1.0 mg/kg diazepam combination increased MRT to an extent comparable to the effect observed at the same dose of diazepam alone. Effects observed with 1.0 mg/kg diazepam and 1.0 g/kg EtOH were similar to those produced by the DZ alone. Combinations of 0.5 g/kg EtOH and 0.5 mg/kg diazepam, 1.0 g/kg EtOH and 0.25 mg/kg diazepam, and 1.0 g/kg EtOH and 0.5 mg/kg diazepam had no significant effect on response times.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMedDate not supplied

Ethanol and chronic diazepam interactions on conflict behavior in rats.

Four groups of five rats each received training on the Geller-Seifter procedure and then received 0.5, 1.0 or 2.0 mg/kg diazepam (DZ) or vehicle, respectively, 15 min prior to the behavior sessions for 14 days. On Day 14 of DZ treatment rats also were administered 2.0 g/kg of ethanol (EtOH) 30 min prior to testing. Significant dose-related decreases in lever pressing occurred between groups over the 13 days of DZ treatment during the pre- and posttone periods. However, a significant effect attributable to days occurred only in the pretone period. During the tone period, the dose-related effects were greater but the variability also increased and specific contrasts between individual means were not significant. The largest increases in lever pressing associated with an anxiolytic effect occurred with 1.0 mg/kg of DZ at Day 6. On Day 14, all animals received 2.0 g/kg of EtOH and their performance was compared to performance on Day 13. During the pre- and posttone periods, the EtOH resulted in significantly less lever pressing in the control, 0.5 and 2.0 mg/kg DZ groups, indicating a sedative effect. Rats treated with 1.0 mg/kg of DZ did not exhibit this EtOH reduction in lever pressing. During the tone or conflict period, a significant dose-related increase in lever pressing due to the EtOH was observed. The increase in the control group was not significant. During repeated exposure to DZ there was a small but significant decrease in number of reinforcements which was enhanced by the EtOH at the 0.5 and 2.0 mg/kg DZ doses but not at 1.0 mg/kg DZ.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMedDate not supplied

Effects of subchronic soman on avoidance-escape behavior and cholinesterase activities.

Male Sprague-Dawley rats were trained on a discriminated avoidance-escape task. They were administered subchronically saline, 12.7 micrograms/kg (0.125 LD50) soman, or 25.5 micrograms/kg (0.25 LD50) soman. Injections were given 5 days per week for 4 weeks. Injections were given subcutaneously immediately following the avoidance behavior test session. Soman produced a reduction in avoidance behavior efficiency in a dose dependent manner. When soman was discontinued, the rats recovered their pre-soman control baselines. Untrained rats given soman according to the same soman regimen were used to measure acetylcholine in brain and cholinesterase activities in brain, blood, and diaphragm. After 18 soman injections at 12.7 and 25.5 micrograms/kg acetylcholine was reduced significantly only in the amygdala. Blood cholinesterase was inhibited as much as 57% after 12.7 micrograms/kg soman and 74% after 25.5 micrograms/kg. Plasma cholinesterase was inhibited to 24% by the 12.7 micrograms/kg dose of soman and to 38% by the 25.5 micrograms/kg dose. Plasma cholinesterase recovered to control levels 11 days after cessation of soman, and whole blood cholinesterase recovered 25 days after cessation of the higher soman dose. Cholinesterase was inhibited significantly in the hippocampus and amygdala in a dose dependent manner. The cholinesterase activities appear to parallel the soman induced decrement in avoidance behavior and the subsequent recovery to control levels following withdrawal of soman.

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PubMedDate not supplied

Effects of 1,1,1-trichloroethane on a match-to-sample discrimination task in the baboon.

1,1,1-trichloroethane was evaluated for its effects on the delayed match-to-sample discrimination task in juvenile baboons. Acute 4-h exposures to 700, 1400, 1800, and 2100 ppm were conducted no more frequently than once a week. Three months later a subchronic exposure to 1200 ppm was conducted over a 7-d period in the same animals. The effects on accuracy of responding were minimal; however, 1,1,1-trichloroethane reduced the number of trials attempted by the animals, reduced the number of extra inconsequential responses during the delay intervals, and increased reaction times. The findings of these experiments illustrate the usefulness of the young baboon as a primate human surrogate model for testing this type of central nervous system depressant.

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PubMedDate not supplied

Exploratory studies of a rodent model for inhalant abuse.

For simulation of inhalant abuse exposure conditions, male and female rats were exposed to high concentrations (10,000-30,000 ppm) toluene vapor until unconscious (8-12 min periods). Sex differences were observed in the mean times to onset of sleep during exposure; linear regression lines of min to sleep onset as a function of toluene/kg body wt had slopes of -0.7492 for males and -0.4515 for females. Animals were removed from the exposure chamber to clean air and both spontaneous horizontal locomotor activity (2/3 animals) and ppm toluene in exhaled air (1/3 animals) were monitored for the first hr post-exposure. Animals regained consciousness within the first 6-7 min and consistently displayed a characteristic pattern of locomotor activity: activity increased initially to 2-3 times baseline level (1 hr preceding exposure) and remained elevated for approximately 10 min; activity then decreased to baseline range for a time before a period of inactivity and/or sleep by 60 min post-exposure. Immediately after regaining consciousness the concentration of toluene exhaled decreased rapidly for the first 10 min, somewhat less rapidly for the next 10-20 min and levelled off at 100-200 ppm for the following 30-40 min. The occurrence and duration of hyperactivity coincided with the period of rapid elimination of unchanged toluene through the lungs.

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