Isodirectional conditioning effects of d-amphetamine and pentobarbital on schedule-controlled operant behavior in pigeons

Pigeons were trained to peck a key on a multi FR30-FI3' schedule. Presession injections of d-amphetamine (2 mg/kg) and pentobarbital (7.5 mg/kg, 10 mg/kg) were paired with presentation of a red light on the ceiling of the operant chamber. After the five pairings separated by two saline sessions in which a white light was lit, the red light was presented without drug injection. The red light came to cause an isodirectional (drug-like) effect on operant behavior. When the red light was paired with drug injections and operant behavior was prevented from occurring, the light did not acquire isodirectional conditioned effect. Thus, responding in the presence of the drug effect is necessary to establish the conditioning.     

Effects of profadol on operant behavior in the pigeon

The effects of profadol were determined on the key pecking of pigeons under the control of a multiple fixed-ratio, fixed-interval schedule of grain presentation. The effects of naloxone and pentobarbital on the behavioral suppression produced by profadol were also determined. Profadol (0.64-10 mg/kg) decreased responding under both schedule components, and the decrease in responding could not be reversed by either naloxone or pentobarbital. A moderate dose of profadol (1.25 mg/kg) was ineffective as an antagonist of morphine (20 mg/kg). Profadol does not produce its behavioral effects in pigeons by an action with a naloxone-sensitive opioid receptor and its non-opioid behavioral effects are dissimilar to those of previously studied meperidine-like phenylpiperidine analgesics.     

Phencyclidine in combination with pentobarbital: Supra-additive effects on complex operant behavior in pigeons

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of four colors. The response chain was maintained by food presentation under afixed ration schedule. Errors produced a brief timeout but did not reset the chain. When phencyclidine was administered alone, the overall response rate decreased and the percent errors increased with increasing doses. Similar effects were found with a high dose of pentobarbital alone. When phencyclidine was administered in combination with pentobarbital dose-effect curves for rate and accuracy shifted to the left as the dose of pentrobarbital was increased. Cobinations of phencyclidine with a high dose of pentobarbital produced supra-additive effects;i.e., the effects on rate and accuracy were greater than expected from simple addition of the effects of each drug given alone. These results extend the generality of previous findings in patas monkeys in a similar repeated-acquisition task.     

The effects of methadone on operant behavior maintained with and without conditioned reinforcement in the pigeon

Effects of methadone on key pecking supplemented with brief stimuli either correlated with or independent of unconditioned reinforcement was investigated. On average, key pecks by pigeons produced brief stimuli (BS) once per minute and food once per 4 min during both components of a multiple schedule (i.e., VI1:BS, VI4:Food). Brief stimuli were paired with food presentation during one component and not related to food during the second component. Acute methadone administration (0.56, 1.0, 1.7, and 3.0 mg/kg) decreased response rates during both components; however, the decrease was smaller by a constant amount during the paired brief stimulus component, regardless of drug dose. These results suggest conditioned reinforcement is not a primary mechanism through which methadone exerts behavioral effects and that reinforcer-correlated stimuli have potential for diminishing the reduced behavioral output observed following methadone administration.     

The effects of methamphetamine and pentobarbital on the running memory span

Summary The effects of two drugs on the running memory span were tested in 18 young men who served as their own control under double blind conditions. Each of the three treatments-methamphetamine, pentobarbital, and saline placebo-was administered intravenously and repeated in a balanced design. Ss were tested on strings of digits, varying in length from 8 to 20 items, the first eight presented at the rate of one item per second, another eight at the rate of one every four sec. The instruction was to reproduce the last five items in the original order.Performance at the slower rate confirms the conclusion of an earlier experiment, conducted at the rate of one digit per two sec., i.e., that pentobarbital narrows and methamphetamine exerts no detectable effect on the running digit span. No significant drug effects were found at the fast rate of presentation.It is proposed that two components determine the running digit span; one involves shifts of attention as the input changes, the other its organization, rehearsal, and other strategies by which the information is stored and made available for recall. Pentobarbital, in the dose used and under the conditions of this study, impairs the latter and does not affect the former.This research was supported in part by a project grant (MH-03996) and research career grants MH 15418 (George A. Talland) and M-1608 (Gardner C. Quarton) from the U.S. Public Health Service.     

Drug effects on an effortful operant: pentobarbital and amphetamine

The behavioral effects of amphetamine and pentobarbital depend upon the conditions maintaining behavior. For example, amphetamine usually decreases the rate of operant behavior maintained by fixed ratio schedules while pentobarbital either increases it or leaves it unaffected. However, when considerable exertion is required, as in situations that require endurance, amphetamine tends to enhance performance while barbiturates degrade it. These differences complicate predictions of the effects of these two drugs on effortful operants. The present experiment was designed to characterize effortful responding behaviorally and pharmacologically. Cebus monkeys were trained to operate a lever by flexing their arms and extending their legs; this response exerted a force approximating their body weight. This operant was maintained by a multiple fixed ratio fixed interval (Mult FR FI) schedule. The two schedules maintained dramatically different response patterns. The FR schedule maintained vigorous, high rate responding characterized by a narrow IRT distribution centered at 0.5 sec. The FI schedule maintained very low overall rates of responding characterized by a variable IRT distribution with a median of 1.5 to 2 sec. Despite very low rates of responding during the FI component, no consistent rate increases appeared after amphetamine, and 0.3 mg/kg eliminated responding altogether. Pentobarbital increased overall rate but also shifted the interresponse time (IRT) distribution toward longer IRTs. The increase in overall rate arose from an earlier onset of responding during the FI component and occurred simultaneously with response slowing. The present studies do not support suggestions of a generalized enhancement of effortful performance by amphetamine or a generalized degradation by pentobarbital.     

Tolerance to suppressive effects of chlordiazepoxide on operant behavior: Lack of cross tolerance to pentobarbital

Pigeons responded under schedules in which either the 60th response (fixed-ratio schedule) or the first response after 3 minutes (fixed-interval schedule) resulted in food delivery. The effects of chlordiazepoxide HCl (1–30 mg/kg) and pentobarbital sodium (1–17 mg/kg) were determined before and during chronic daily exposure to either 10 or 17 mg/kg chlordiazepoxide—doses that markedly suppressed responding when given acutely. After about three weeks of daily injections of chlordiazepoxide, there was at least a three-fold shift to the right of the dose-effect curve for chlordiazepoxide, but not consistent change in the effects of pentobarbital.     

Effects of pentobarbital,lysergic acid diethylamide and chlorpromazine on matching behavior in the pigeon

Summary A report is given of the effects of three drugs on matching-to-sample behavior in pigeons. Pentobarbital produced considerable initial decrements in accuracy, with relatively fast recovery to normal levels. With lysergic acid diethylamide, an initial period of inactivity, during which the birds did not respond to the experimental task, was followed by essentially normal performance. Chlorpromazine effects showed considerable variability both within and across subjects.This research was carried out at Columbia University, under support from Grant MY-3673 from the Institute of Mental Health, U.S. Public Health Service.     

Interactions of morphine and nalorphine with physostigmine on operant behavior in the rat

Morphine and nalorphine were tested alone and in combination with physostigmine (0.0625 mg/kg) in rats trained under a continuous avoidance schedule with an escape contingency. When tested alone, nalorphine increased avoidance rate in doses up to 32 mg/kg but exerted no other effects. Morphine, 1 mg/kg, increased avoidance response rate while higher doses produced a graded depression of all behavior. In the presence of physostigmine, nalorphine produced a well-defined graded depression of avoidance responding and increased the number of shocks received by the animals over a 16-fold dose range. Physostigmine failed to potentiate the prominent depressant effects of morphine in the same test situation. The finding that in the presence of cholinesterase inhibition nalorphine acts as a depressant of operant behavior in the rat supports existing evidence that cholinergic mediation should be considered as a factor in some of the actions of strong analgesics.Publication No. 1028 of the Division of Basic Health Sciences of Emory University. This investigation was supported by USPHS Grants SO-1-FR05364 and MH12870-04.A preliminary report of this investigation appeared in Fed. Proc, 30, 390 (1971).Postdoctoral trainee of NIH Graduate Pharmacology Training Grant GM-179 during part of this work.     

Effects of sodium pentobarbital on complex operant discriminations

Summary Results are reported for the effects of sodium pentobarbital on (a) zero delay matching-to-sample, (b) simultaneous oddity, and (c) variable delay matching-to-sample. In all these situations there are decrements in accuracy with increasing dose levels. The oddity performance proved to be considerably less sensitive to the drug effects than zero-delay matching. In variable delay matching there was no clear evidence for any relationship between the magnitude of the drug effect and the length of the delay interval.This research was carried out at Columbia University with support from Grant MH-03673 from the National Institute of Mental Health, U. S. Public Health Service.     

Chronic effects of lead on schedule-controlled pigeon behavior

Pigeons were trained to peck a response key under a multiple fixed ratio 30 response (FR 30) fixed-interval 5-min (FI 5) schedule of food presentation. When rates of responding stabilized, lead acetate (6.25, 12.5, and 25 mg/kg body weight) or sodium acetate solutions were given daily by gastric intubation. Blood-lead concentrations were measured weekly by atomic absorption spectrometry, and responding under the multiple schedule was measured Monday through Friday. Control intubations of sodium acetate did not affect responding under either component of the schedule. The 25-mg/kg dose of lead decreased rates of responding after 3 to 10 days of administration and usually was lethal between 18 and 35 days. Post mortem examination of the birds showed obvious esophageal dilatation, damage to the crop, weight loss, and subarachnoid hemorrhages. Administration of the 25-mg/kg dose was discontinued in some birds after responding had ceased. Responding gradually began to recover, but rates of responding remained low and variable under both components of the schedule for many days. Daily administration of the 12.5-mg/kg dose of lead caused one death, but no obvious signs of intoxication occurred in the other birds. However, three of the four birds surviving daily 12.5-mg/kg doses of lead showed decreased rates of responding under both schedule components within 30 days of the initial intubation. The fourth bird showed a highly variable rate under the FI component of the schedule during lead administration; however, when lead administration was discontinued, dramatic increases in rates of responding above lead pretreatment levels occurred, particularly under the FI component. These rate increases persisted for 75 days thereafter. The 6.25-mg/kg dose of lead produced only small changes in rates of responding during 70 days of intubation. Blood-lead concentrations were very high (150–3470 μg/dl) during treatment with all doses of lead. Increasing doses produced increasing blood concentrations which were correlated with increasing behavioral effects, although correlations between blood-lead concentrations and behavioral changes were low within individual birds.     

Time-response effects of pimozide on operant behavior and schedule-induced polydipsia

Previous research has indicated that the administration of specific doses of pimozide results in the suppression of the acquisition of schedule-induced polydipsia in rats while not affecting operant behavior. The purpose of this study was to determine if these results were due to a specific action of pimozide on schedule-induced polydipsia or if they were due to an insufficient presession time of drug administration. Pimozide at 1.0 mg/kg was administered to three groups of rats at either 30, 60 or 120 minutes presession with control subjects receiving administration of the drug vehicle also at these times. The results of the study were that both operant behavior and the acquisition of schedule-induced polydipsia were affected in a nondifferential and time-dependent manner by pimozide. It was also found that pimozide caused an alteration in the temporal pattern of both schedule-induced polydipsia and operant responding. This latter result appears to have been caused by a disruption in sensorimotor integration due to the dopamine blocking properties of pimozide.     

Antagonism between physostigmine and atropine on the behavior of the pigeon

Summary The effects of physostigmine upon food-maintained operant behavior of the pigeon were investigated. Physostigmine completely suppressed responding for a period up to 180 minutes and small doses of atropine could antagonize this suppression. Neostigmine produced a similar suppression of behavior of shorter duration. Methylatropine, much less potent than atropine in antagonizing behavioral suppression by physostigmine, was more potent in antagonizing neostigmine. Nicotine produced a suppression of behavior similar to that produced by the two anticholinesterases, but neither methylatropine nor atropine antagonized this effect. These findings support the general supposition that suppression of behavior by physostigmine is in part mediated by muscarinic receptors in the central nervous system.With 5 Figures in the TextDedicated to Professor Otto Krayer on his 65th birthday.Thus study was supported by grants MH-02645, MH-02094 and 2M-7084 from the United States Public Health Service.     

Tolerance to ethanol's disruptive effects on operant behavior in rats

The effects of pre-session and post-session daily ethanol injections on the development and loss of tolerance to ethanol's effects on fixed ratio operant performance in rats was assessed using a cumulative dosing procedure. Daily pre-session ethanol administration produced a greater decrease in ethanol sensitivity than did daily post-session ethanol. Both tolerance effects persisted for at least 1 month after the chronic injection phase. No changes in ethanol sensitivity were apparent in the saline control group and no changes in estimated blood ethanol levels were found after the chronic treatments. The post-session ethanol groups displayed a performance decrement during the initial segment of the chronic injection period, but improved significantly across the chronic phase. These data suggest that some delayed effect of ethanol initially impaired performance but that tolerance to this ethanol effect also occurred and probably contributed to the decline in ethanol sensitivity seen in these groups. Compensatory learning as the mechanism for tolerance development in the pre-session and post-session ethanol groups was supported by the finding of no change in ethanol sensitivity in rats exposed to comparable daily ethanol without any concurrent operant task on which the direct, immediate, or indirect, delayed ethanol effects could operate.     

Assessment of pimozide's motor and hedonic effects on operant behavior in rats

The present study examined the effects of the neuroleptic pimozide on several measures of motor capacity and reinforcement efficacy in rats trained to respond according to a multiple random interval (RI) food reinforcement schedule (mean interreinforcement intervals of 10, 20, 40, 80, and 160 sec). Pimozide (0.125, 0.25, 0.5, and 1.0 mg/kg) produced a dose-dependent suppression of response rates for all five RI schedules and a dose-dependent increase in response duration. An independent measure of motor activity in photocell activity chambers also was decreased by pimozide in a dose-dependent manner. Photocell activity was significantly correlated with response duration and with the Matching Equation parameter k. Thus, all three measures of motor performance revealed similar decreases in motor capacity at the high dose of pimozide. Reinforcement efficacy also was reduced by the 1.0 mg/kg dose of pimozide as indicated by an increase in the Matching Equation parameter Re. The parameters k and Re were not significantly correlated, suggesting that these two Matching Equation parameters do provide independent measures of motor capacity and reinforcement efficacy, respectively. The present results demonstrate the importance of obtaining measures other than simple response rates in order to assess drug effects on operant behavior.     

Differential effects of phencyclidine and MDA on complex operant behavior in monkeys

In one component of a multiple schedule, patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four geometric forms (learning). In the other component, the four-response chain was the same each session (performance). The response chain in each component was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. With increasing doses of phencyclidine the overall response rate in each schedule component decreased, the percent errors in each component increased, and there was less within-session error reduction (acquisition) in the learning component. MDA (3,4-methylenedioxyamphetamine), a hallucinogen that is self-administered in nonhuman primates, was similar to phencyclidine in producing dose-related rate-decreasing effects in both schedule components. Unlike phencyclidine, however, MDA had little or no effect on accuracy in either learning or performance.     

Comparative effects of ethanol on motor activity and operant behavior.

Ethanol effects on two types of motor activity and on lever responding for food delivered on a fixed-ratio 20 (FR 20) reinforcement schedule were compared using C57BL/6 (C57) mice. Low doses of ethanol (1-2 g/kg) transiently elevated horizontal activity and high doses (2.5 and 3.0 g/kg) reduced this behavior throughout testing with a slight recovery toward the end of a 16-min test period. In contrast, similar ethanol doses produced a monotonic reduction in both vertical activity and lever responding for food under the FR 20 schedule. The ethanol-induced reduction in FR 20 lever responding was less prolonged than the reduction in vertical activity but was more prolonged than the reduction in horizontal activity. Because vertical activity and lever responding for food delivered on the FR 20 schedule were never elevated, were reduced at ethanol doses that either stimulated or depressed horizontal activity, and were unaffected by low ethanol doses that did not affect horizontal activity, it is unlikely that either are sensitive to the stimulatory effects of ethanol. Accountable mechanisms for the different effects of ethanol on the three behaviors are unknown; however, the present study eliminates ethanol dose, postinjection time, testing time, and food deprivation condition as possible reasons for the differences.     

A comparison of the effects of opiate antagonists on operant and ingestive behavior

Previous studies have found that naloxone and other opiate antagonists will decrease the food and water intake of experimental animals. The present study investigated the possibility that these effects may be due to a generalized action of opiate antagonists to block an endogenous reward system. A direct comparison was made between the effects of naloxone and naltrexone on FR responding maintained by small quantities of milk and on the consumption of milk when it was freely available. Both drugs reduced milk consumption at all doses (0.3–30 mg/kg) but produced only small decreases in FR response rates at the highest doses. These results do not support the view that the actions of opiate antagonists on eating and drinking represent an inhibitory action on central reward mechanisms.