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Effects of azaprophen, scopolamine and trihexyphenidyl on schedule-controlled behavior, before and after chronic physostigmine.

The effects of the muscarinic acetylcholine receptor antagonists, azaprophen (0.3-10.0 mg/kg), scopolamine (0.01-3.0 mg/kg) and trihexyphenidyl (0.3-10.0 mg/kg) were examined in rats using a VI 18 s schedule of food reinforcement, before and after chronic physostigmine administration. All three compounds produced dose-dependent decreases [corrected] in the rate of responding. Scopolamine was more potent than trihexyphenidyl which was equipotent to azaprophen. All three compounds antagonized the response rate-decreasing effects of physostigmine in a dose-dependent fashion. Following 43 consecutive daily administrations of physostigmine (0.4 mg/kg), partial tolerance developed to its response rate-decreasing effects. When the three antagonists were again examined (alone and in combination with physostigmine), their effects were generally unchanged. These results further characterize the behavioral effects of azaprophen, scopolamine and trihexyphenidyl. These results also suggest that tolerance to physostigmine's effects can be mediated through behavioral rather than pharmacological mechanisms.

Acetylcholine↗

Emotions and cognitions associated with bingeing and weight control behavior in bulimia.

The examination of cognitions and emotions during the bulimic cycle is critical in understanding possible maintenance factors involved in bulimia. In this study, 22 bulimics and 22 nonbulimics recorded their thoughts and feelings every 2 waking hours over a 6-day period. Bulimics additionally recorded their moods and thoughts during their binges and compensatory behaviors (e.g., purging, exercise). Higher levels of negative affect were reported at all stages of the cycle compared to baseline, although negative affect decreased after the compensatory behavior stage. Subjects also reported stronger distorted cognitions before and after the binge compared to baseline. One of the distorted cognitions (feeling fat) decreased in strength after subjects engaged in compensatory behavior. Additional analyses revealed that most levels of negative affect and distorted cognitions were elevated prior to binges as compared to meals. Finally, negative affect and distorted cognitions were stronger after binges than after meals.

Adult↗

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↗

Tolerance to oxotremorine's effects on schedule-controlled behavior in physostigmine-tolerant rats.

Tolerance to the effects of physostigmine and oxotremorine in rats was evaluated using a multiple fixed-ratio 10, extinction schedule of food presentation. Physostigmine was administered either once daily or three times daily for 18 consecutive days. Tolerance to physostigmine's response decreasing effects was observed under both administration regimens. Cumulative dose-effect functions for oxotremorine (0.0056-0.562 mg/kg) were determined before and after chronic physostigmine administration. Oxotremorine's potency to produce response rate suppression decreased in rats receiving physostigmine three times daily but did not substantially change in rats receiving single daily injections. These results demonstrate that the dose or duration of action of physostigmine can determine whether tolerance to physostigmine's effects is accompanied by cross-tolerance to oxotremorine's effects.

Animals↗

Effects of ketazocine, ethylketazocine and phenazocine on schedule-controlled behavior: antagonism by naloxone.

Dose-effect curves were determined for phenazocine (0.64-2.5 mg/kg), ketazocine (1.25-80 mg/kg) and ethylketazocine (1.25-80 mg/kg) in pigeons responding under a multiple fixed-ratio 30-response, fixed-interval 5-min schedule of grain presentation. All three opioid agonists decreased responding with the larger doses. The effects of phenazocine were completely antagonized by small doses of naloxone (0.01-1 mg/kg), whereas the effects of ethylketazocine required larger doses of naloxone (1-10 mg/kg) to be completely antagonized. The behavioral effects of ketazocine were partially attenuated by naloxone, but were not antagonized completely even by a 10 mg/kg dose of naloxone. These data from the pigeon are consistent with previous interpretations that the effects of phenazocine are mediated by actions at a mu opioid receptor, whereas the effects of ketazocine and ethylketazocine are mediated by actions at a kappa opioid receptor.

Analgesics, Opioid↗

Comparison of the effects of antipsychotic drugs on the schedule-controlled behavior of squirrel monkeys and pigeons.

Lever pressing by squirrel monkeys and key pecking by pigeons were maintained under a multiple 3-min fixed-interval (FI), 30-response fixed-ratio (FR) schedule by the presentation of food. These responses, which differed under the two schedules, but were similar for both species, were used to compare the effects of antipsychotic compounds from different pharmacological classes. Except for differences in potency levels, the effects of intermediate doses of haloperidol and molindone were similar in monkeys and pigeons; these compounds decreased responding under the fixed-interval schedule at doses that did not affect fixed-ratio responding. Similar effects also occurred with chlorpromazine, promazine and thiothixene in pigeons. With monkeys, however, intermediate doses of promazine decreased fixed-ratio responding more than responding maintained under the fixed-interval schedule, while chlorpromazine and thiothixene produced similar effects on responding under both schedules. The effects of novel antipsychotic, clozapine, differed from those of the other agents in both monkeys and pigeons. With both species clozapine increased fixed interval responding at doses that did not affect responding under the fixed-ratio schedule. Doses required to reduce responding at least 50% were approximately 5 to 160 times greater for pigeons than for monkeys for all drugs except clozapine which was equipotent in both species. In monkeys the order of potency was haloperidol greater than molindone = thiothixene greater than chlorpromazine greater than clozapine greater than promazine, whereas in pigeons the order was haloperidol greater than thiothixene greater than clozapine greater than molindone greater than promazine greater than chlorpromazine.

Animals↗

Effects of MK-212 (6-chloro-2[1-piperazinyl]pyrazine) on schedule-controlled behavior and their reversal by 5-HT antagonists in the pigeon.

The effects of MK-212 (6-chloro-2[1-piperazinyl]pyrazine), a centrally-active 5-hydroxytryptamine (5-HT; serotonin) agonist, were studied alone and in combination with the 5-HT antagonists, methysergide (0.01-0.1 mg/kg), metergoline (0.01-1.0 mg/kg) and ketanserin (0.01-3.0 mg/kg). Pigeons were maintained under a procedure where key pecks were reinforced under a multiple fixed-interval (FI) fixed-ratio (FR) schedule of food presentation. In the fixed-interval component, the first response after 3 min had elapsed, produced food, while in the fixed-ratio component, the thirtieth response was reinforced. The drug MK-212 (0.1-3.0 mg/kg) produced dose-related decreases in response rates under both components of the schedule. In smaller doses of MK-212 (0.3 and 1.0 mg/kg), the decrease in the response rate was greater in the fixed-interval component than in the fixed-ratio component. Small doses of methysergide (0.03 mg/kg) and metergoline (0.1 mg/kg), which had little effect when given alone, partially blocked the effects of MK-212 (1.7 and 3.0 mg/kg) in decreasing rate. Larger doses of these compounds, which sometimes increased the response rate when given alone, resulted in a more complete restoration of response rates when administered with MK-212. Ketanserin, a selective 5-HT2 antagonist, reversed the effects of MK-212 in some cases, but the patterning of responses remained disturbed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of selected analogs of adenosine on schedule-controlled behavior in rats.

Acute administration of N6(L-phenylisopropyl)adenosine (L-PIA; 0.01-0.178 mg/kg, s.c.), N6-cyclohexyladenosine (CHA; 0.01-0.178 mg/kg, s.c.), 2-chloroadenosine (2-CA; 0.32-0.56 mg/kg, s.c.), N6-cycloheptyladenosine (CHPA; 0.032-1.0 mg/kg, s.c.), N6-phenyladenosine (PA; 0.1-1.0 mg/kg, s.c.), N6(D-phenylisopropyl)adenosine (D-PIA; 0.32-1.0 mg/kg, s.c.) and N6-benzyladenosine (BA; 1.0-17.8 mg/kg, s.c.) produced dose-related decreases in responding under a fixed-ratio (FR) schedule of food reinforcement. Dose-effect curves were determined by administering cumulative doses (s.c.) during periods that preceded the sequential components of the schedule. Neither 2-chloroadenine arabinoside (2-CAB) nor 2',5'-dideoxyadenosine (2',5'-DDA) altered fixed-ratio responding at the doses studied (0.1-3.2 and 1.0 and 3.2, respectively). Caffeine (0.32 and 3.2 mg/kg) antagonized the behavioral effects of L-PIA in a dose-related, surmountable manner. Daily administration of L-PIA (0.1 mg/kg) resulted in the development of tolerance to the effects of L-PIA decreasing rate and cross-tolerance to other analogs of adenosine (CHA, BA, D-PIA). No cross-tolerance was produced to caffeine, levorphanol or chlordiazepoxide. The activity and order of potency of the analogs of adenosine tested were consistent with the effects of agonists at A1 adenosine receptors. Furthermore, the results demonstrate that the behavioral effects of N6- and 2-chlorine-substituted analogs of adenosine probably act through similar CNS mechanism(s).

Adenosine↗

Lateralization of visually controlled behavior in pigeons.

Pigeons were trained binocularly on two different successive pattern discrimination tasks. After reaching criterion they performed the tasks with either the left or the right eye occluded or with both eyes unobstructed. The number of responses emitted was greater when the right rather than the left eye was uncovered. Also the percent correct discrimination scores were better when seeing with the right eye than with the left one. Some pigeons originally acquired the discrimination monocularly, generally using the right eye, although both eyes were uncovered. The results are discussed in relation to brain structures that may mediate this performance.

Animals↗

Exercise-induced changes in schedule controlled behavior.

This experiment was designed to measure the direct effect of acute exercise on performance of an operant task in rats. Treadmill exercise was manipulated along two dimensions: speed and duration. Separate groups of rats (n = 12) were tested under a multi-component time-out fixed-ratio (MULT TO FR) schedule following four exercise treatments. The first group of animals (Group A) ran at a constant speed for four different periods of time. A second group (Group B) ran for a constant period of time at four different treadmill speeds. For both groups, running took place just before operant test sessions. Operant responding on test days was compared with operant responding on the immediately preceding day. Both exercise duration and exercise speed had significant effects on operant performance.

Animals↗