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At least 307 records · Page 17Linked to original sources
PubMed1979

Naloxone effects on schedule-controlled behavior in morphine-pelleted rats.

The effects of morphine pellet implantation and naloxone administration were examined in rats lever pressing under inter-response time schedules of food presentation. Subcutaneous implantation of a morphine pellet initially decreased lever-pressing rates. Tolerance to this effect developed within 3--4 days. Naloxone (0.25--1.0 mg/kg) decreased response rates in morphine-pelleted rats in a dose-dependent and time-dependent manner. All doses of naloxone severely decreased rates of lever pressing on days four to nine post-pellet. This rate-decreasing effect persisted 7--17 days for 0.25 mg/kg naloxone, 9--22 days for 0.50 mg/kg, and 13--28 days for 1.0 mg/kg. Decreases in response rate were due to an increased frequency of long pauses and not to marked shifts in the temporal patterning of those lever presses that did occur. Changes in response rate after naloxone were accompanied by body weight loss. Area values summarizing the naloxone-induced changes in response rate or body weight over time after pellet implantation increased as a function of naloxone dose. Naloxone (0.25--1.0 mg/kg) did not alter performance by placebo-pelleted rats.

Animals↗
PubMed1980

Schedule-controlled behavior in the morphine-dependent and post-dependent rat.

Chronic morphine treatment has been reported to induce long-lasting changes in the responses of animals to the subsequent administration of morphine or narcotic antagonists. However, there have been few systematic studies in which the effects of morphine or narcotic antagonists have been compared in the same group of animals before, during, and after chronic morphine administration. Rats were trained to press a lever on a variable interval (1 min) schedule of food presentation and dose-response curves were determined for morphine (0.3--30 mg/kg) and naloxone (0.003--10 mg/kg) in the same group of animals prior to, during, and following morphine dependence. Dependence was induced and maintained by scheduled access to 0.05% morphine drinking solution for 10 min every 6 h. Response rates and fluid intake remained constant over the 9 month study. The dose-response curves for morphine and naloxone in predependent and dependent animals were similar to those previously reported in studies using other schedules of reinforcement and different techniques for establishing morphine dependence: chronic morphine treatment produced a threefold decrease in the effect of morphine and a dramatic increase in the effectiveness of naloxone in decreasing response rate. The altered sensitivity of dependent rats to morphine and naloxone was completely reversed in the post-dependent animals, within 4 weeks after the withdrawal of morphine. Scheduled access to a morphine solution affords a simple means of maintaining morphine-tolerant and dependent animals for long-term behavioral studies.

Animals↗
PubMed1985

Schedule-controlled behavior as an index of the development and loss of ethanol tolerance in the rat.

Twelve male Sprague-Dawley rats, following training on one of two food-motivated operant schedules (Fixed-Ratio 30 or Variable Interval 30 s), were exposed to an escalating regimen of daily ethanol (1.125-3.0 g/kg, IP) administration. This increasing dose regimen continued until the maximally tolerable dose for each subject was reached. Tolerance was then monitored for approximately 6 months by periodic ethanol challenge doses (1.5 g/kg). Dose-effect curves (DECs) were obtained prior to chronic ethanol (DEC1), immediately after ethanol tolerance development (DEC2), and 6 months (DEC3) following termination of ethanol exposure. At DEC1, ethanol produced dose-dependent decreases in rate on both schedules with no significant schedule differences in ED50 (the dose effective at reducing the maximal response rate by one-half) values. Maximal tolerance was achieved in means of 46 and 55 days on the VI and FR schedules, respectively. Differences in rate of tolerance acquisition on the initial dose of the chronic regimen (1.125 g/kg) account for most of the difference in the overall rate of acquisition. Comparison of the ED50 data from DECs 1 and 2 indicated that daily ethanol exposure resulted in a 2-fold decrease in ethanol sensitivity (i.e., tolerance) on both operant schedules. The ED50 data from DECs 1 and 3 demonstrated a 1.7-fold decrease in ethanol potency on DEC3. This duration of tolerance was considerably longer than that generally reported, and possibly related to the extended ethanol exposure and the sensitivity of operant schedules to drug effects.

Animals↗
PubMed1981

Effects of chronic delta 9-tetrahydrocannabinol administration on schedule-controlled behavior of pigeons: cross-tolerance to pentobarbital and barbital.

Pigeons responding under a variable-interval (VI) 75-s schedule of food presentation were used to study cross-tolerance from delta 9-tetrahydrocannabinol (delta 9-THC) to pentobarbital and barbital. After initial dose-effect functions for pentobarbital and barbital were determined, the birds received delta 9-THC injections for 6 weeks. This chronic administration regimen resulted in a greater than 100-fold tolerance to delta 9-THC. Redetermination of the pentobarbital and barbital dose-effect functions during the chronic delta 9-THC regimen revealed statistically significant shifts to the right for the pentobarbital (0.191 log unit) and barbital (0.078 log unit) dose-effect curves. All six birds showed tolerance to pentobarbital, while four of the six showed tolerance to barbital. Blood barbital levels before and after chronic delta 9-THC was more prolonged and of much greater magnitude than the cross-tolerance to pentobarbital or barbital. The results demonstrate that cross-tolerance can develop from delta 9-THC to a barbiturate that normally undergoes little metabolism.

Animals↗
PubMed1982

Effects of dopamine uptake inhibitors on schedule-controlled behavior in the squirrel monkey.

Squirrel monkeys responded under a multiple fixed-interval (FI) fixed-ratio (FR) schedule of stimulus-shock termination. Benztropine mesylate (0.03-1.7 mg/kg), bupropion HCl (0.3-5.6 mg/kg), mazindol (0.01-0.3 mg/kg), and nomifensine maleate (0.1-1.0 mg/kg) markedly increased responding under the FI schedule, but not under the FR schedule. Mazindol was about three-times more potent than nomifensine and ten-times more potent than bupropion. Benztropine and mazindol were about equal in potency. The order and relative magnitude of potency differences for mazindol, nomifensine, and bupropion are similar to those reported by others for in vitro inhibition of dopamine uptake in rat striatum, but the relative potency of benztropine was greater in these behavioral experiments than expected from its potency in inhibiting dopamine uptake.

Animals↗
PubMed1982

Tolerance to the disruptive effects of arecoline on schedule-controlled behavior.

The roles of dispositional, physiological, and behavioral factors in the development of tolerance to the effects of arecoline on operant behavior were assessed. In Experiment I, rats were trained to press a lever on a variable-interval 15-s schedule for milk reinforcement. Dose-effect relationships were assessed prior to and during chronic arecoline (1.74 mg/kg/day) treatment. After 21 days of arecoline administration prior to each session, the dose-effect relationship for total number of responses did not shift. However, the dose-effect relationship for total number of reinforcers shifted to the right. In Experiment II, rats were trained to respond on a fixed-ratio 20 schedule for milk reinforcement. Dose-effect relationships were assessed prior to and during chronic arecoline (0.87 mg/kg/day) administration. One group of rats received daily injections of arecoline prior to the session and a second group received arecoline injections 30 min after the session. Daily administration of arecoline resulted in a greater shift to the right of the dose-effect relationship for the presession group than it did for the postsession group. These data demonstrate the importance of behavioral factors in the development of tolerance to arecoline.

Animals↗
PubMed1991

Effects of sigma receptor ligands on schedule-controlled behavior of rats: relation to sigma and PCP receptor binding affinity.

Eleven drugs were examined for their ability to inhibit sigma and phencyclidine (PCP) receptor binding, as labelled by (+)[3H]-R-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP), [3H]ditolylguanidine (DTG), (+)[3H]N-allylnormetazocine (NANM) and [3H]1-(1-(2-thienyl)cyclohexyl)piperidine (TCP), in membrane preparations from whole rat brain. The same drugs were studied for their effects under a fixed-ratio (FR) schedule of food reinforcement in rats. The relative potency order of the drugs for decreasing FR responding was: haloperidol greater than (+)-3-PPP greater than (-)NANM greater than BMY 14802 greater than PCP greater than (+)NANM greater than DTG greater than rimcazole greater than JO 1783 greater than JO1784 greater than (-)butaclamol. The binding affinities of all 11 drugs for either the [3H]DTG, (+)[3H]-3-PPP, (+)[3H]NANM or [3H]TCP site did not correlate significantly with the potencies of the same drugs for decreasing FR behavior. Rimcazole, (+)-3-PPP and haloperidol, at behaviorally inactive doses, were studied for their effects as antagonists of the rate-decreasing effects of JO 1784, DTG and (+)NANM: rimcazole attenuated the effects of DTG and (+)NANM but not JO 1784; (+)-3-PPP attenuated the effects of (+)NANM but not JO 1784 and DTG; and haloperidol was devoid of antagonistic actions. Moreover, BMY 14802 did not attenuate the rate-decreasing effects of (+)-3-PPP. These results further indicate that it is difficult to distinguish between purported sigma agonist and antagonist drugs.

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↗
PubMed2001

Spontaneous activity as a contingency-controlled behavior within an operant context: alprazolam concentration-effect relations after subcutaneous administration in rats.

RATIONALE: Environmental factors affect serum drug concentration-effect relations. For example, after midazolam administration, longer pre-session delays imposed in experimental chambers produced differential concentration-effect relations compared to those of shorter delays. OBJECTIVES: To evaluate the extent to which serum concentrations determine alprazolam's effects on spontaneous activity in the presence and absence of a differential reinforcement of low rate (DRL 45-s) contingency using pharmacokinetic-pharmacodynamic analysis. Serum concentrations reported here were simulated from our published pharmacokinetic parameters for alprazolam. METHODS: One group (n=8) was used to investigate alprazolam's effects on spontaneous activity within the DRL contingency by placing an activity platform beneath each operant chamber to monitor concurrently both spontaneous activity (large and small movements) and DRL performance (shorter-response and reinforcement rates) in 3-h sessions; a parallel group (n=7) was used without the operant context. The concentration-effect relation of the reinforcement rate was compared and contrasted with those of spontaneous activity. RESULTS: Alprazolam decreased large and small movements within the DRL contingency, which corresponded to that of reinforcement rates under the DRL 45-s schedule. In contrast, without the DRL contingency, alprazolam's effects on small movements were short-lived (i.e., 30 min) and no effects on large movements were detected. Hence, the predicted concentration-effect relations for the reinforcement rate function described those of spontaneous activity well within the operant context, but not those without the operant context. Furthermore, the latter showed no correlation between serum alprazolam concentration and large movements; a significant, but low negative correlation for small movements was observed. CONCLUSIONS: The duration of alprazolam's action was dependent on not only dose size but also the behavioral measure examined. By imposing the DRL contingency, spontaneous activity behaves as an ideal pharmacodynamic measure (i.e., continuous, sensitive, and objective).

Algorithms↗
PubMed1975

Single cell activity in the auditory cortex of the unanesthetized, behaving monkey: correlation with stimulus controlled behavior.

The neural activity of 60 cells in the auditory cortices of two rhesus monkeys was examined in relation to systematic variations in cued reinforcement conditions. Subjects were trained on a variant of the auditory reaction time (RT) task. In the final behavioral paradigm monkeys were rewarded for rapid key releases to all tonal stimuli in one reinforcement condition (frequency irrelevant = FI), while in the other stimulus-cued condition (frequency discrimination = FD) releases to certain tonal test frequencies were unrewarded. Upon completion of behavioral training, RTs to identical tonal test stimuli were longer and more variable when presented in the unrewarded (FD) condition. Following neurosurgery it was possible to observe the effects of reinforcement condition on auditory RT performance and the activity of single auditory cortical cells simultaneously. Of the auditory cortical cells sampled, 25% showed definite and repeatable alterations in evoked activity to the same tonal stimulus which were correlated with reinforcement condition. For nearly all cells examined the influence of reinforcement condition was much the same: on excitatory responses were increased in the FD condition. A few of the cells also showed alterations in latency and/or pattern of evoked discharge. Importantly, none of the units examined showed changes in their spontaneous discharge rates as a function of reinforcement condition. both peripheral mechanical and central neural theories were considered as a basis for the observed neural alterations. The specificity and latency of the alterations as well as the absence of tonic effects seemed to indicate that the neural changes observed were mediated by central mechanisms. Our results strongly suggest that the activity of a sample of auditory cortical neurons depends on the behavioral state of the preparation. We propose that 'behavioral state", appropriately defined, can be a useful concept for neurophysiologists.

Action Potentials↗
PubMed1982

Attenuation of normeperidine's suppressing effect on schedule-controlled behavior.

The purpose of the present study was to compare several central nervous system (CNS) depressant drugs in their ability to attenuate the suppressant effects of normeperidine on the responding of pigeons under a multiple fixed-ratio, fixed-interval schedule of grain presentation. The effects of pentobarbital (3 and 10 mg/kg i.m.), diazepam (1-10 mg/kg p.o.), clonazepam (0.03-3 mg/kg p.o.), aminooxyacetic acid (1-10 mg/kg i.m.), baclofen (5 and 10 mg/kg i.m.) and ethanol (0.5-2 g/kg p.o.) were determined alone and in the presence of 17.5 mg/kg (p.o.) of normeperidine, a dose which almost completely eliminates responding. Pentobarbital, diazepam and clonazepam attenuated the normeperidine-induced suppression of behavior, whereas aminooxyacetic acid, baclofen and ethanol failed to attenuate the effects of normeperidine. The results indicate that in the pigeon the non-opioid effects of normeperidine and related analogs are related to proconvulsive actions.

Animals↗