PubMed Health⌕ Search

Biomedical subjects

N Hymowitz

Publications and source records attributed to N Hymowitz.

At least 37 records · Page 2Linked to original sources

Effect of soman on schedule-controlled behavior and brain acetylcholinesterase in rats.

Rats were trained to press a lever under a multiple fixed-ratio 25 fixed-interval 50-second (FR25 FI50-sec) schedule of food reinforcement. Soman, 70-90 micrograms/kg, s.c., suppressed response rates in both components, with a slightly greater effect in the FI schedule. The pattern of responding under the FI schedule, however, was maintained until lever-pressing was nearly completely suppressed. At the highest doses, soman occasionally caused tremors or mild tonic seizures with hindlimb abduction. The suppression of response rate was correlated with inhibition of acetylcholinesterase (AChE) in all brain regions examined: cortex, striatum, hippocampus, hypothalamus and brainstem. Cortical AChE was inhibited to the highest degree, while striatal AChE was most resistant to inhibition by soman.

Acetylcholinesterase↗

Inhibition of acetylcholinesterase in the gut inhibits schedule-controlled behavior in the rat.

Rats were trained to press a lever under a multiple Fixed-Ratio 25 Fixed-Interval 50-second schedule of food reinforcement. Subcutaneous injection of soman, 80 micrograms/kg, suppressed responding under both schedules and inhibited acetylcholinesterase (AChE) in the brain. AChE activity in the gastrointestinal tract was not significantly inhibited. In contrast, i.p. injection of either soman (10-40 micrograms/kg), neostigmine (75 micrograms/kg) or DFP (350 micrograms/kg) caused marked suppression of behavior and AChE activity of the gut, without affecting brain AChE. These doses caused marked increases in peristaltic activity and likely caused gastrointestinal spasm. Injection of DFP, 500 micrograms/kg, s.c., inhibited AChE in both the brain and gut. The results indicate that inhibition of AChE in the gastrointestinal tract by certain anticholinesterase agents may be involved in the behavioral effects attributed to these drugs.

Animals↗

Effect of repeated intraperitoneal injections of soman on schedule-controlled behavior in the rat.

Intraperitoneal (IP) administration of the acetylcholinesterase inhibitor, soman (10-40 micrograms/kg), suppressed in a dose-related manner response rates in rats maintained under a multiple fixed-interval 50-s fixed-ratio 25 schedule of food delivery. Chronic administration of soman at weekly intervals resulted in tolerance to the response. When soman administration was separated by 2-5 weeks in individual rats, the suppressive effects of the agent again became apparent. Analysis of acetylcholinesterase activity revealed that enzyme inhibition was limited to gastrointestinal areas near the site of injection. There was no significant effect on brain acetylcholinesterase even following IP injection of doses which completely suppressed responding. The IP route may be useful for studying tolerance and other chronic effects of soman without producing generalized toxicity.

Acetylcholinesterase↗

Effects of selective central muscarinic blockade on schedule-controlled behavior and on the rate-decreasing effects of physostigmine.

N-(4-diethylamino-2-butynyl)-succinimide, or DKJ-21, is a muscarinic receptor antagonist with a high degree of selectivity for the central nervous system. In the present study of 6 rats maintained under a fixed-interval 50-sec schedule of food reinforcement, atropine and methylatropine reduced responding in a dose dependent manner, while DKJ-21 had little or no effect. Our findings suggest that the suppression caused by atropine and methylatropine may be the result of the dry mouth induced by these agents. Doses of DKJ-21 which had no effect on schedule performance antagonized the rate-lowering effects of physostigmine in all of the animals. Neither atropine nor methylatropine consistently antagonized the inhibitory effects of physostigmine. Some antagonism may be inferred, however, from the findings that response rates were suppressed less by combinations of atropine and physostigmine than by either drug alone.

Animals↗

Effects of diazepam on responding suppressed by response-dependent and independent electric-shock delivery.

While the effects of benzodiazepines on punished responding (response-dependent shock) are straightforward and unambiguous, their effects on behavior suppressed by response-independent shock are conflicting and inconsistent. Some investigators reported that benzodiazepines either have no effect on, or suppress further, responding during response-independent shock, while others reported that benzodiazepines enhance response rates during independent shock delivery in the same manner as during dependent shock. The present study compared the effects of diazepam on rates of lever pressing maintained by a variable-interval 35-sec schedule of food delivery in rats exposed alternately to fixed-interval 180 sec (response-dependent) and fixed-time 180 sec (response-independent) schedules of shock delivery. Diazepam increased punished responding in a dose-dependent manner for each animal. "Rate-dependency," degree of suppression and presence of external stimuli influenced rate-enhancement by the drug. Effects of diazepam on responding suppressed by response-independent shock were inconsistent, with two animals revealing rate enhancement comparable to punished responding, and two others revealing further increases in response suppression. Reasons for the differential effects of diazepam on response-rates suppressed by the two forms of shock delivery remain obscure, although the basic phenomenon seems to be real and not merely an artifact of "rate-dependency."

Animals↗

Effects of diazepam on schedule-controlled and schedule-induced behavior under signaled and unsignaled shock.

Schedule-controlled lever pressing and schedule-induced licking were studied in rats under a multiple fixed-interval fixed-interval schedule of food reinforcement upon which was superimposed a multiple variable-time variable-time schedule of electric-shock delivery. Shocks were signaled in one component of the multiple schedule and unsignaled in the other. The effects of diazepam upon the suppression of behavior during the signal (conditioned suppression) and during signaled and unsignaled shock (differential suppression) were studied under several shock intensities (Experiment 1) and at increased body weight (Experiment 2). In each study, diazepam led to dose-dependent increases in the rate of pressing and licking during signaled and unsignaled shock, but had little effect on conditioned suppression. the rate-enhancing effects of diazepam depended upon the intensity of shock, nature of the response, and whether or not shocks were signaled. The data was discussed in terms of (1) implications for understanding the effects of signaled and unsignaled shock on behavior, (2) the effects of diazepam on behavior suppressed by response-independent shock, and (3) comparison between operant and schedule-induced behavior.

Animals↗

Effects of salsolinol, a tetrahydroisoquinolone alkaloid, on multiple schedule performance in rats.

Rats were trained to lever press under a multiple fixed-ratio fixed-interval schedule of food reinforcement. Intracerebroventricular injections of salsolinol (1-methyl-6,7-dihydroxytetrahydroisoquinoline), a condensation product of dopamine and acetaldehyde, caused a dose-related decrease in fixed-ratio responding over a dosage range of 15-120 microgram. In contrast, fixed-interval responding was only reduced at the 120 microgram dose and was increased in two of the animals after injection of 15-30 microgram of salsolinol.

Alkaloids↗

Effects of electric-shock delivery on schedule-induced water intake: delay of shock, shock intensity, and body-weight loss.

In each of four experiments, schedule-induced water intake in the rat was studied under fixed-time 40-sec food delivery. Experiments I and II studied the temporal relationship between response-independent electric-shock delivery and licking. Shock was delivered under a variable-time 60-sec schedule. A lick-dependent delay was imposed so that licking and shock delivery were systematically separated in time by a minimum of 1 to 15 sec. Over a wide range of shock intensities the data failed to reveal a consistent delay-of-shock effect. Similar shock intensities led to similar reduction of water intake at each delay of shock interval. Experiments III and IV studied the effects of body-weight loss on water intake during independent shock delivery. In Experiment III, shock was delivered under variable-time 60-sec with a minimum separation between shock and licking of 5 sec. In Experiment IV, shock was delivered under variable-time 180-sec. The minimum separation between shock and licking was 10 sec. In each study, the resistance of water intake to suppression by shock delivery increased as the degree of body-weight loss increased. Schedule-induced water intake was affected more by shock when the animal was maintained at 90% of free-feeding weight than at 70%.

Animals↗