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R F Genovese

Publications and source records attributed to R F Genovese.

6 recordsLinked to original sources
PubMed1992

Perceptual bisection in rats: the effects of physostigmine, scopolamine and pirenzepine.

The effects of cholinergic drugs on three different perceptual bisection tasks were studied in rats. Physostigmine (0.056-0.56 mg/kg), a reversible anticholinesterase, produced dose-dependent decrements in discriminability (A'), but did not affect the bisection point (BP) in visual duration, auditory duration, and auditory intensity bisection tasks. This finding is consistent with results previously obtained in an auditory duration bisection task with an irreversible anticholinesterase, diisopropyl phosphofluoridate. Scopolamine (0.075-0.422 mg/kg), a muscarinic cholinergic-receptor antagonist, produced dose-dependent decrements in both A' and BP in visual and auditory duration bisection tasks. The behavioral antagonism between physostigmine (0.56 mg/kg) and scopolamine (0.075-0.237 mg/kg) was studied in the visual and auditory duration bisection tasks. The BP was not affected by physostigmine alone or in combination with scopolamine, except at the largest dose of scopolamine, which produced a reliable decrement in the BP. A', however, was equally decreased by physostigmine alone and all combinations of physostigmine and scopolamine. Pirenzepine (1, 3 and 10 mg/kg), a selective high-affinity M1 muscarinic antagonist, had no effect on A' or the BP in the duration bisection tasks, suggesting changes in perception produced by muscarinic antagonists do not involve the M1 receptor subtype. The similar drug effects in different sensory modalities (visual and auditory) and perceptual systems (subjective duration and loudness) suggest that cholinergic drugs may affect perceptual mechanisms responsible for sensory coding, such as the output of a neural generator.

Animals↗
PubMed1992

Evaluation of transient forebrain ischemia induced by four vessel occlusion using schedule-controlled behavior.

Transient (5-min) global forebrain ischemia, induced by four- vessel occlusion, was assessed using a multiple fixed-ratio, fixed-interval schedule of food presentation in five rats. Under control conditions, the schedule produced distinctive response rates in each schedule component. Initially, ischemia disrupted responding under both schedule components, and to approximately the same degree. In general, total session responses returned to pre-occlusion levels during the course of 45 post-occlusion days, however, response rates under the fixed-interval component showed slightly less recovery than those under the fixed-ratio component. Histological assessment revealed considerable variability in hippocampal damage between rats. Severe damage in the CA1, CA2, and CA3 formations was observed in a single rat, and that rat also showed the greatest degree of response disruption. These results suggest that schedule-controlled responding may be a valuable method for assessing the effects of ischemic injury, and thus, putative neuroprotective compounds, on complex behavior.

Animals↗
PubMed1992

Behavioral effects of some diphenyl-substituted antimuscarinics: comparison with cocaine and atropine.

To more fully characterize the behavioral excitatory effects observed with certain diphenyl-substituted antimuscarinics, various behavioral effects of benactyzine, a prototype excitatory antimuscarinic, was evaluated in rats. These effects were compared to those of cocaine, atropine, and azaprophen, a muscarinic antagonist that contains both the diphenyl substituents of benactyzine and a ring isomeric with the tropane ring of atropine. Under a fixed-interval 5-min schedule of food presentation, cocaine and benactyzine increased response rates. Atropine and azaprophen only decreased responding. The muscarinic agonist oxotremorine attenuated the rate-increasing effects but did not alter the disruptions in the temporal patterning produced by benactyzine or shift the dose-effect function to the right. In rats discriminating 10 mg/kg cocaine from saline, benactyzine partially substituted for cocaine, producing a maximum of 50% cocaine-appropriate responses. Benactyzine fully substituted for scopolamine in rats discriminating 0.056 mg/kg scopolamine from saline. All antimuscarinics increased locomotor activity when activity levels were low in control animals, but the increases were less than those produced by cocaine. Cocaine increased both locomotor activity and fixed-interval responding at comparable doses, whereas 10-fold higher doses of benactyzine were required to increase locomotor activity. These results support the following conclusions: 1) In addition to its classical antimuscarinic behavioral profile, benactyzine has behavioral excitatory actions similar in some respects to those of cocaine; 2) the behavioral excitatory effects of benactyzine do not appear to be due solely to antagonism of muscarinic receptors; and 3) the alkyl-ester may be an important structural feature of diphenyl-substituted antimuscarinics for the induction of behavioral stimulation.

Animals↗
PubMed1991

Effects of MK-801 stereoisomers on schedule-controlled behavior in rats.

Behavioral effects of (+)MK-801 (0.03-0.32 mg/kg) and (-)MK-801 (0.32-3.20 mg/kg) were evaluated in rats using a multiple fixed-ratio, fixed-interval (FR20, FI2) schedule of food presentation. Both enantiomers produced dose-dependent decreases in response rate under the FR20 and in this respect (+)MK-801 was approximately ten times as potent as (-)MK-801. Under the FI2 schedule component, the (+) enantiomer produced substantial increases as well as decreases in response rate whereas the (-) enantiomer produced only decreases. When 0.178 mg/kg (+)MK-801 and 1.78 mg/kg (-)MK-801 were administered for 11 consecutive days, tolerance developed to the decrease in response rate under the FR20 schedule component. Tolerance to the effects of the (+) enantiomer under the FI2 schedule component was indicated by progressively larger increases in response rate than those observed during acute administration. These results support potential therapeutic applications of MK-801.

Animals↗