Roy J. Hartmann

Effects of acetone and toluene vapors on multiple schedule performance of rats

Six rats were trained to press a lever for a liquid food reward on a multiple fixed ratio--fixed interval (FR--FI) schedule of reinforcement. When lever-pressing rates became relatively stable, the animals were exposed to 150 ppm of either acetone or toluene for duration times of 1/2, 1, 2 and 4 hr. Exposures were conducted at least three weeks apart. Acetone produced minimal changes on the FR--FI responding during the 1/2 hr exposure. During the 1 hr exposure period, both FR and FI rates increased while during the 2 hr exposure, both FR and FI responses decreased below control levels. During the 4 hr exposure FI responses approximated control levels for 2 rats and were above the control level for the third animal while FR rates were below controls for 2 of the 3 subjects. Rate changes under toluene were generally qualitatively similar to those produced by acetone. An initial enhancement of FR and FI rates occurred during the shorter exposure periods followed by a decrease in rates during the longer exposure periods.

Toluene inhalation and anxiolytic activity: Possible synergism with diazepam

Toluene exposures or injections of diazepam reinstated lever responses that had been suppressed by punishment in laboratory rats. When concentrations of toluene or diazepam that were ineffective or minimally effective in this paradigm were administered in combination, they produced a qualitatively similar effect which was much greater than the sum total of effects produced by the same amount of either substance alone. These observations suggest an anxiolytic action for toluene and a possible synergism between the two substances.

Neurobehavioral effects of repeated sublethal soman in primates

Juvenile male baboons were trained to perform a match-to-sample discrimination task; effects of repeated sublethal exposure to the organophosphate nerve gas, soman, upon task performance were then explored. Both acute and subchronic exposure schedules were employed, and soman potency was verified by assay of soman-induced inhibition of acetylcholinesterase activity in whole blood, plasma, and erythrocytes. A characteristic profile of behavioral effects encompassing immediate, persistent, and delayed effects was observed. Immediate dose-related effects of soman included: increases in mean session response time, increases in errors, and decreases in extra responses. Seizures were also observed at the highest dose of soman employed (5 micrograms/kg). The increase in mean session response time was due to intermittent lapses in responding to stimuli (attentional deficits). Both the attentional deficits and intermittent generalized seizures were also persistent effects, with both occurring randomly after acute exposure to 5 micrograms/kg soman. Preliminary evidence suggests that occurrence of attentional deficits was associated with the occurrence of generalized and/or focal seizures; and that these effects may reflect irreversible lesions which become more threatening to the animal with increasing time. An additional, delayed effect was a sudden marked increase in the incidence of extra inconsequential responses which occurred several weeks after cessation of soman exposures.

Blockade of 5-HTP reduction of ethanol drinking with the decarboxylase inhibitor, Ro 4-4602

5-Hydroxytryptophan (5-HTP) reduced ethanol intake in laboratory rats. The reduction of ethanol intake was blocked when Ro 4-4602, the decarboxylase inhibitor, was given in combination with the 5-hydroxytryptophan. These observations provide further support for the involvement of brain serotonin in voluntary ethanol drinking by the rat.

Effects of acetone, methyl ethyl ketone and methyl isobutyl ketone on a match-to-sample task in the baboon ☆

Acetone, methyl ethyl ketone (MEK) and methyl isobutyl ketone (MIBK) were evaluated for effects on a delayed match-to-sample discrimination task in the juvenile baboon. The animals were exposed to 1/2 the threshold limit value (TLV) of each gas for 24 hr per day during a 7-day period. They were also exposed to a combination of MEK and MIBK at the same exposure concentrations. Each exposure condition affected accuracy of performance minimally but resulted in increased and decreased extra responses during the delay intervals. Response times were slowed under acetone, MEK or MIBK. In contrast to the effects of the individual gases, exposure to a combination of the same doses of MEK and MIBK produced a consistent increase in extra responses during delay and a concomitant decrease in response times. Changes in tissue uptake and metabolism are suggested as possible mechanisms to explain this observation.

P-chlorophenylalanine effects on a conditioned emotional response in rats

Abstract Hungry rats learned to press a lever for a liquid food reward on a 2-minute variable-interval schedule of reinforcement. Lever pressing was suppressed in the presence of a tone stimulus by pairing the tone with brief electric shocks. p-Chlorophenylalanine, the tryptophan hydroxylase inhibitor, produced an attenuation of the conditioned suppression. The effect was reversed in same animals by administration of 5-hydroxytryptophan.

Acute soman effects in the juvenile baboon: Effects on a match-to-sample discrimination task and on total blood acetylcholinesterase

Male juvenile baboons, trained on a match-to-sample operant discrimination task, were given acute intramuscular injections of soman (methyl pinacolyl phosphonofluoridate) at 1.0, 2.0, 3.0, 4.0, and 5.0 micrograms/kg. The different doses were given in a mixed order just before a behavioral test session. Just prior to administration of each soman dose and immediately following the 2-hr behavioral test session, a sample of blood (0.5 ml) was drawn from the baboon and analyzed for inhibition of acetylcholinesterase activity. Thereafter, blood sampling was accomplished at weekly intervals and soman was administered again only when whole blood acetylcholinesterase reached at least 80% of pre-soman control level. Behavioral effects of soman included a slowing of response times, a decrease in extra inconsequential responses, a decrease in responsiveness to the visual stimuli and an increase in errors. These effects were observed when acetylcholinesterase (AChE) levels fell to 25 mumoles/hr/ml blood or less. The threshold dose for behavioral effects was very close to the dose of soman which induced seizures.

Toluene and ethanol effects on baboon match-to-sample performance: Possible synergistic action ☆

Four juvenile male baboons were trained to respond for banana pellet rewards on a match-to-sample discrimination task. Exposure of the animals to a range of concentrations of either toluene or ethanol vapor resulted in a slowing of response times and a reduction in the percent trials attempted for some concentrations of either vapor. When behaviorally ineffective (subthreshold) concentrations of each vapor were combined, effects upon response times and trials attempted were similar to the effects produced by the higher concentrations of the individual vapors. However, while high concentrations of ethanol vapor produced errors in half of the subjects, combinations of ethanol and toluene did not increase this effect. This information suggests an ethanol potentiation of toluene effects, rather than the reverse.

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.

Alteration of ethanol preference in hamsters: effects of photoperiod and 5-hydroxytryptophan.

Relatively few investigators have made use of the golden hamster as an experimental animal for ethanol studies. This is somewhat surprising insofar as hamsters show a marked preference for ethanol solutions in free-choice experiments. Given a choice of water or a 10% ethanol solution, hamsters will drink 88% of their total fluid as ethanol solution (Arvola and Forsander, 1961). Furthermore, the most preferred concentration of ethanol for the male hamster is 15% (Arvola and Forsander, 1963) in contrast to the rat that shows a preference only for much lower ethanol concentrations.