Cholinergic modulation of an opposed effect of d-amphetamine and methylphenidate on the rearing response

Rats given d-amphetamine (1 mg/kg) engage in frequent, short-duration rearing responses, whereas rats given methylphenidate (1 mg/kg) make less frequent, long-duration responses. The effects on this behavior of mixing d-amphetamine or methylphenidate with scopolamine or physostigmine suggest that this opposed action on rearing response duration is related to cholinergic-catecholaminergic balance. The anticholinergic agent scopolamine produces changes in rearing response duration similar to those produced by d-amphetamine, while the cholinergic agent physostigmine lengthens response duration and further potentiates this effect of methylphenidate.     

Effects of d-amphetamine,scopolamine, chlordiazepoxide and diphenylhydantoin on self-stimulation behavior and brain acetylcholine

The effects of d-amphetamine (0.25–8), scopolamine (0.25–8), chlordiazepoxide (2.5–40), and diphenylhydantoin (25–75), given i.p. or s.c. on a mg/kg basis, were studied on self-stimulation behavior in the male albino rat. The dose-effect relationships, the role of baseline rates of responding and their effects on brain acetylcholine (ACh) were determined in rats trained to self-stimulate for electrical reward in the lateral posterior hypothalamus. The effects of d-amphetamine were both dose and baseline-rate dependent. Low-moderate doses (0.5–2.0 mg/kg inclusive) facilitated self-stimulation and larger doses (2.0 to 8.0 mg/kg) depressed responding. Baseline rates before d-amphetamine administration were extremely important in the effect observed. Low rates of responding were facilitated and high rates were depressed by this agent. The effects of scopolamine in a wide range of dosage were less consistent. A small dose (0.5 mg/kg) facilitated only transiently self-stimulation and larger doses (1–8 mg/kg) tended to depress this behavior. Baseline rate effects were less important but high-rate responders were usually depressed by scopolamine.The effects of chlordiazepoxide were dose-dependent. A dose of (5 mg/kg) caused facilitation but larger doses (10–40 mg/kg) produced depression of selfstimulation irrespective of baseline rates. However, high-rate stimulators showed the most dramatic increases with 5 mg/kg of chlordiazepoxide. In contrast, diphenylhydantoin (25–75 mg/kg) usually depressed self-stimulation. Low rate self-stimulators showed the most marked depressant effects.Brain ACh was progressively reduced by handling of naive animals, injection of saline, and 1/2 h of self-stimulation and escape behavior. Animals not allowed to self-stimulate but given d-amphetamine (2.0 mg/kg), scopolamine (2.0 mg/kg) showed a significant decrease in brain ACh. Self-stimulation, in addition to medication with the various drugs, showed a trend for further reduction in brain ACh but the differences were not statistically significant.Supported in part by Grant MH-11846 (to EID) and MH-11627 (to JO), U.S. Public Health Service.     

Effects of chlordiazepoxide,oxazepam, chlorpromazine,andd-Amphetamine on sexual responses in male and female hamsters

The acute effects on sexual behavior of oxazepam (16–64 mg/kg), chlordiazepoxide (8–64 mg/kg), chlorpromazine (2–8 mg/kg), andd-amphetamine (0.8–3.2 mg/kg) were examined in intact male and female golden hamsters (Mesocricetus auratus). Intraperitoneal injections were given 45 min before the first behavioral test. In 10-min tests lordosis was observed in estrous females both before and after copulation, and mounts, intromissions, and ejaculations were observed in males. Dose-response related decrements in male sexual behavior were observed following chlorpromazine and chlordiazepoxide. All dose levels of oxazepam depressed male sexual behavior. The highest dose of chlordiazepoxide and oxazepam attenuated the onset of female sexual behavior, and all dose levels reduced postcopulatory lordosis durations. Amphetamine did not interrupt either male or female sexual behavior, and chlorpromazine disrupted male but not female behavior.     

Noradrenergic and cholinergic action on neuronal activity during self-stimulation behavior in the rat

The effects of drugs with adrenergic and cholinergic actions were studied in unanaesthetized, freely behaving rats. Pairs of drugs—of which the first in each pair suppressed responding and the second one reinstated it—were tested in rats during self-stimulation behavior while effects on neuronal activity correlated with this behavior were determined. Two types of neuronal responses were studied. The first was the occurrence of spikes with fixed latencies in relation to stimulation applied in the posterior lateral hypothalamus. The second was the suppression of spontaneously active neurons as a function of stimulation in the posterior lateral hypothalamus. The first type of response was studied in the cingulate, the preoptic and the ventral midbrain regions. The second type was studied in the middle hypothalamus.The drugs with adrenergic action were tetrabenazine and (+)-amphetamine; the drugs with cholinergic action were physostigmine and scopolamine. The second drug in each pair was administered 30 min after the first one and at the time of maximal effect of the first drug on self-stimulation behavior.Tetrabenazine reduced spike activity with fixed latencies in the ventral midbrain region, but not in the cingulate and the preoptic regions at the time when it suppressed self-stimulating behavior. Amphetamine partially restored the frequency of spikes with fixed latencies in the midbrain region at the time when it reinstated self-stimulation behavior. Tetrabenazine reduced the suppressant effect of stimulation in the posterior hypothalamus (disinhibition) on neuronal activity in the middle hypothalamus. Amphetamine reinstated partially the suppressant action of stimulation on neuronal activity recorded in the middle hypothalamus at the time it reinstated self-stimulation behavior.Physostigmine and scopolamine produced the identical effects of tetrabenazine and amphetamine on self-stimulation behavior, but they were ineffective on neuronal activity.     

Effects of chlorpromazine, chlordiazepoxide and pentobarbital on neuronal excitability in the medial forebrain bundle during self-stimulation behavior

The effects of chlordiazepoxide, chlorpromazine and pentobarbital were studied on self-stimulation behavior and simultaneously on neuronal responses driven by the rewarding stimuli. The tests were carried out on rats implanted with microelectrodes in the medial forebrain bundle for recording extracellular potentials and with macroelectrodes in the posterior lateral hypothalamus for producing self-stimulation behavior. The neuronal responses were (1) an excitatory response in the anterior hypothalamus, and (2) an inhibitory response in the middle hypothalamus. Chlordiazepoxide (20 mg/kg), chlorpromazine (4 mg/kg) or pentobarbital 10 mg/kg) were given intraperitoneally to suppress self-stimulation. (+)-Amphetamine (2 mg/kg) was given 30 min after the first compound to restore self-stimulation.

The results showed that chlordiazepoxide and pentobarbital acted nonspecifically on the excitatory response by reducing the spontaneous rate of firing at the time when self-stimulation was suppressed. Chlorpromazine abolished the driven excitatory responses in the anterior hypothalamus which were correlated in a 100% fashion with self-stimulation behavior. All three compounds had insignificant effects on the inhibitory responses.

The results give some basis for supposing that the effects of chlorpromazine were indices of effects on neuronal activity mediating positive reinforcement.     

Interactions of chlordiazepoxide and anorectic agents on rate and duration parameters of feeding in the rat

d-Amphetamine (0.5 and 1.0 mg/kg) and dl-fenfluramine (2.0 and 4.0 mg/kg) reduced food intake in a short exposure feeding test, and their effects were counteracted by chlordiazepoxide, particularly at 5.0 mg/kg. Chlordiazepoxide reduced latency to eat, extended the duration of feeding and depressed the rate of feeding. Antagonism occurred in combination with d-amphetamine in relation to latency and duration, but in this experiment d-amphetamine did not affect feeding rate. Antagonism also occurred in combination with fenfluramine, with latency and duration measures, but only at the lower chlordiazepoxide dose. Instead, chlordiazepoxide (10.0 mg/kg) enhanced fenfluramine's effects to reduce feeding duration and feeding rate.     

Effects of drugs on behaviour of aggressive mice

1 The occurrence of 11 aggressive and non-aggressive activities was observed in aggressive male mice treated with drugs in paired interactions with non-aggressive males given water. Effects of chlordiazepoxide, diazepam, barbitone, chlorpromazine, imipramine, (+)-amphetamine, lysergic acid diethylamide (LSD) all given orally and of intraperitoneal scopolamine were investigated.2 Scopolamine (0.25 and 0.75 mg/kg), (+)-amphetamine (0.25 and 1 mg/kg), chlorpromazine (2.5 mg/kg), diazepam (10 mg/kg) and chlordiazepoxide (50 mg/kg) reduced aggressive activities (attacks, aggressive unrest) without inhibiting walking across the cage or rearing in the aggressive mice. Thus, the inhibition of aggression induced by these drugs does not seem to be due to neuromuscular impairment and seems to this extent specific. On the other hand, imipramine lessened aggressive activities only at a dose (80 mg/kg) which also decreased walking across the cage and rearing. Barbitone or LSD did not change aggression at either dose tested (20 and 60 or 0.01 and 1 mg/kg, respectively). Aggressive activities were increased significantly only by chlordiazepoxide at a dose of 5 mg/kg.3 (+)-Amphetamine (0.25 mg/kg) and scopolamine (0.75 mg/kg) increased escapes and alert postures, respectively, in the aggressive mice.4 Diazepam and chlordiazepoxide decreased tail rattling at 1 and 5 mg/kg, respectively, doses 10 times lower than those inhibiting attacks. The other drugs tested inhibited tail rattling only at doses reducing attacks. Tail rattling appears to be a convenient measure for testing effects of drugs on behavioural conflict.5 Diazepam (5 and 10 mg/kg), chlordiazepoxide (20 and 50 mg/kg), barbitone (60 mg/kg) and scopolamine (0.25 and 0.75 mg/kg) increased sociable activities (sniffing, following partners and climbing over them) whereas (+)-amphetamine, chlorpromazine, imipramine and LSD did not. Effects of the drugs on sociable activities in aggressive mice seem to correlate with their action on punished responding and other types of suppressed behaviour.     

Psychotropic drug influences on brain acetylcholine utilization

The cholinergic antisynthesis agent HC-3 was given intraventricularly to young male rats 20–30 days old to deplete brain acetylcholine (ACh). The rate of HC-3 induced depletion of ACh was used as an index of ACh utilization. Total brain ACh was determined following various doses of chlordiazepoxide, pentobarbital, chlorpromazine, methotrimeprazine, imipramine, morphine, d-amphetamine, scopolamine, LSD-25, and phencyclidine given i.p. alone and after intraventricular administration of HC-3. It was found that psychotropic drugs have marked differential effects on the rate of HC-3 induced ACh depletion.Supported in part by grant MH-11846, USPHS.     

Cork gnawing in the rat as a screening method for buspirone-like anxiolytics

Male Long-Evans rats were individually allowed access to No. 11 corks for 30 min per day. After 30 sessions, the mean amount gnawed away, 0.10 g per session, was stable enough to allow drug testing; it reached asymptote at 0.03 g after 140 sessions. Drugs were injected PO 30 min before testing, except as noted. On the asymptotic baseline, the novel anxiolytic buspirone (8–32 mg/kg) and its congener gepirone (8–32 mg/kg) produced large, doserelated increases in cork gnawing. The standard anxiolytics chlordiazepoxide (16–32 mg/kg) and meprobamate (128 mg/kg, 60 min pretreatment) and the new sedative zopiclone (4–32 mg/kg) also produced substantial increases. Diazepam, oxazepam, and alprazolam produced marginal increases, and pentobarbital had no effect at behaviorally relevant doses. The non-anxiolytics d-amphetamine, chlorpromazine, acute imipramine, morphine (IP), and valproic acid either decreased or did not change cork gnawing. Phencyclidine (IP) and scopolamine produced marginal increases. Apomorphine (5 mg/kg SC) produced intense stereotyped gnawing of cage mesh but abolished gnawing of cork. Cork gnawing is proposed as a simple, economical behavioral method to identify buspirone-like anxiolytics.     

Discriminative stimulus properties of d-amphetamine-pentobarbital combinations

Pigeons were trained to discriminate IM injections of 1.0 mg/kg d-amphetamine from water, 5.6 mg/kg pentobarbital from water, or 1.0 mg/kg d-amphetamine from 5.6 mg/kg pentobarbital by requiring them to peck different response keys depending on which substance was administered prior to the session. Excellent stimulus control was achieved under all conditions with close to 100% of the responses occurring on the injection-correlated key. In tests with doses different from those used in training, the percentage of responses on the drug key was directly related to drug dose. When d-amphetamine was given to birds trained to discriminate pentobarbital from water or when pentobarbital was given to birds trained to discriminate d-amphetamine from water, responding occurred predominately on the water-correlated key. d-Amphetamine produced a dose-related antagonism of the effects of pentobarbital for birds trained to discriminate pentobarbital from water or from d-amphetamine. Rates of responding on the drug key were generally highes after administration of the drug doses used in discrimination training; but response rates were not systematically related to the percentage of responses occurring on the drug key. All birds were subsequently trained to discriminate a combination of 1.0 mg/kg d-amphetamine and 5.6 mg/kg pentobarbital from either 1.0 mg/kg d-amphetamine or 5.6 mg/kg pentobarbital alone, demonstrating that the discriminative stimulus properties of amphetamine-pentobarbital combinations are different from either drug alone. Several of the drug effects reported were related to the drug discrimination that had been established.Portions of this paper were reported at the 49th annual meeting of the Eastern Psychological Association, Washington, D.C., 1978     

Failure of naloxone to modify the effects of chlorpromazine and d-amphetamine on avoidance behavior in the squirrel monkey

Lever-pressing by squirrel monkeys was maintained under a continuous avoidance schedule in which each response postponed for 30 s the delivery of an electric shock to the tail. Dose-response curves were determined for chlorpromazine (0.03–0.3 mg/kg) and d-amphetamine (0.03–1.0 mg/kg) administered alone and administered concomitantly with 1.0 or 10 mg/kg of aaloxone. The dose-response curves for chlorpromazine and d-amphetamine were similar to those previously reported for monkeys under other schedules of shock-maintained behavior: Chlorpromazine decreased responding in a dose-related manner while d-amphetamine increased responding at low doses and disrupted behavior at the highest dose. Naloxone did not modify the effects of chlorpromazine, and d-amphetamine. These results suggest that interactions observed previously between naloxone and nonopiate drugs on behavior in pigeons and rodents are not general phenomena in all animal species.     

Attenuation by pimozide of the suppressant effect of d-amphetamine on operant behaviour

The interaction between pimozide (a selective D₂-dopamine receptor antagonist) and d-amphetamine on the operant performance of rats maintained under variable-interval schedules of positive reinforcement was examined. In Experiment 1, eight rats responded under variable-interval 30-s and variable-interval 300-s. Pimozide (0.0625, 0.125, 0.25, 0.5 mg/kg) suppressed performance maintained under both schedules in a dose-dependent manner, the degrees of suppression being equivalent in the two schedules. In Experiment 2, 12 rats responded under the same schedules. d-Amphetamine (0.1–3.2 mg/kg) suppressed performance under both schedules, the degree of suppression being somewhat greater in the case of variable-interval 30-s. Pre-treatment with pimozide (0.0625, 0.125 mg/kg) significantly attenuated the suppressant effect of d-amphetamine under both schedules. It is suggested that D₂-dopamine receptors may be involved in mediating the suppressant effect of d-amphetamine on operant behaviour.     

The effects of d-amphetamine,chlordiazepoxide and alpha-flupenthixol on food-reinforced tracking of a visual stimulus by rats

Rats were trained to respond to one of two levers under a random ratio schedule of food reinforcement. Which of the levers was correct was redetermined before each response and signalled by a light. The effects of d-amphetamine (0.2–3.2 mg/kg), chlordiazepoxide (1–8 mg/kg), and the neuroleptic alpha-flupenthixol (0.03–0.33 mg/kg) on the efficiency of rats tracking this visual cue were examined. d-Amphetamine increased the proportion of responses made on the correct lever at low and intermediate doses, but reduced the proportion at 3.2 mg/kg. At the highest dose, chlordiazepoxide produced a small increase in this measure, together with a reduction in response rate, but alpha-flupenthixol had no effect, even at a dose reducing response rate. Low doses of amphetamine also increased switching between the levers, producing a proportionately greater increase in switching from the correct lever to the incorrect lever than vice versa. The results are interpreted as showing that d-amphetamine facilitates tracking performance as a result of its action of enhancing response switching, and supporting the hypothesis that facilitation of performance by amphetamine-like drugs depends on the effect of the drug on response output coinciding with task requirements.     

Interactions of naloxone with morphine,amphetamine and phencyclidine on fixed interval responding for intracranial self-stimulation in rats

Rats were implanted with stimulating electrodes aimed at the medial forebrain bundle-lateral hypothalamus (MFB-LH) and were trained to lever-press for brain self-stimulation on a fixed interval: 60 s schedule of reinforcement. The effects of graded doses of naloxone (0.1–30 mg/kg), morphine (0.3–5.6 mg/kg), naloxone plus morphine,d-amphetamine (0.03–1.0 mg/kg), naloxone plusd-amphetamine, phencyclidine (0.3–5.6 mg/kg), and naloxone plus phencyclidine were tested. Naloxone produced a significant decrease in rates at 30 mg/kg. Naloxone (0.1–1.0 mg/kg) plus morphine blocked the dose-dependent decrease produced by morphine alone. In contrast, naloxone (1.0–10 mg/kg) plusd-amphetamine attenuated the graded increase in response rates produced byd-amphetamine. Naloxone (1.0–10 mg/kg) plus phencyclidine did not reliably change the increase in response rates produced by phencyclidine alone. The use of the fixed interval schedule of brain self-stimulation to study these drug interactions is novel, and further demonstrates that the highly reinforcing aspects of brain stimulation, known to be influenced by dopamine, may also be modulated by the endogenous opiate system.     

Effects of hypothalamic self-stimulation of drugs influencing dopaminergic neurotransmission injected into nucleus accumbens and corpus striatum of rats

The role of the nucleus accumbens septi (ACB) and corpus striatum (CPU) in self-stimulation were investigated by injecting directly or indirectly acting stimulant drugs or a dopamine-(DA-) receptor blocking agent into each site bilaterally. d-Amphetamine (68 nmol) facilitated hypothalamic self-stimulation when injected into either site. Apomorphine (40 nmol) depressed or facilitated responding, the direction and magnitude of this effect being contingent (C=0.52) on the effect of systemic injection (0.3 mg/kg i.p.), and correlated with the difference between the effects of d-and l-amphetamine (0.5 mg/kg i.p.) but not with injection site. Haloperidol (6.6 nmol) in either site depressed self-stimulation. Tyramine (730 nmol), an agent believed to cause noncontingent displacement of transmitter from catecholamine terminals, depressed self-stimulation when injected into CPU, but facilitated it when injected into ACB. The sitespecific effects found with tyramine but not with apomorphine may have been due to release by tyramine of transmitters other than DA.     

A brief brain ischemia produces morphological damage of hippocampal CA1 pyramidal cells without affecting the sensitivities of psychoactive drugs in two types of discrete avoidance tasks in Mongolian gerbils

Effects of subcutaneous administration of psychoactive drugs: methamphetamine (0.13-1 mg/kg), chlorpromazine (0.5-2 mg/kg), physostigmine (0.05-0.2 mg/kg), scopolamine (0.031-0.5 mg/kg), pentobarbital (5-20 mg/kg), diazepam (0.5-2 mg/kg) and morphine (1.3-5 mg/kg) on discrete lever-press and shuttle avoidance responses were investigated in Mongolian gerbils that had received a brief (5 min) bilateral brain ischemic operation. Although some of the ischemic animals tended to show a retardation of acquisition of the avoidance responses, the established baselines were almost identical between the sham-operated and ischemic groups. In the lever-press task, morphine increased the response rate, whereas chlorpromazine, physostigmine, pentobarbital and diazepam decreased both the response and avoidance rates in a dose-dependent manner. In the shuttle avoidance task, both the response and avoidance rates were dose-dependently increased by methamphetamine, scopolamine and morphine, but chlorpromazine, physostigmine, pentobarbital and diazepam dose-dependently decreased them. These drug effects were almost the same between the sham-operated and ischemic groups. However, the ischemic-operation produced a significant loss of pyramidal cells in the CA1 sector of the hippocampus, the remaining level being less than 10% that of the sham-operated control animals.     

Influence of naloxone upon motor activity induced by psychomotor stimulant drugs

Naloxone, an opioid receptor antagonist, attenuates a wide range of behavioral effects ofd-amphetamine, such as the stimulation of motor activity. To investigate the pharmacological selectivity of the naloxone/amphetamine interaction, we assessed the effects of naloxone (5.0 mg/kg SC) upon motor activity induced in rats by a range of psychomotor stimulant drugs with a mechanism of action either similar to or different from that ofd-amphetamine. Each of the drugs tested caused dose-dependent increases in both gross and fine activity. Naloxone attenuated the gross but not the fine activity response tod- andl-amphetamine, but had no influence upon the other catecholamine-releasing drugs, methamphetamine and phendimetrazine. In contrast, naloxone increased the gross but not the fine activity response to the catecholamine uptake inhibitors cocaine and mazindol, but had no effects upon the motor response to methylphenidate. The responses to other stimulant drugs (apomorphine, caffeine, scopolamine) were unaffected by naloxone pretreatment. The present findings extend the range of conditions under which naloxone and, by inference, endogenous opioid systems, modulate the behavioral response to psychomotor stimulants. However, the differential effects of naloxone upon the motor response to individual stimulant drugs support previous suggestions of fundamental differences in mechanisms of action among these compounds.     

Comparison of the effects of morphine,pentazocine, cyclazocine and amphetamine on intracranial self-stimulation in the rat

Rats were trained to press a lever in order to stimulate their lateral hypothalamus through a chronically implanted electrode. Dose-response curves were determined for the effects of morphine (0.3–10 mg/kg), pentazocine (1.0–30 mg/kg), cyclazocine (0.03–3.0 mg/kg) and d-amphetamine (0.1–3.0 mg/kg) on responding for intracranial stimulation, and then were redetermined in the presence of one or two doses of naloxone. The three analgesics produced only dose-related decreases in responding with the following relative potencies: cyclazocine>morphine>pentazocine. The well-documented rate-increasing effects of d-amphetamine on intracranial self-stimulation were observed at 0.3 and 1.0 mg/kg of the drug; decreases in responding at 3.0 mg/kg were associated with stereotyped behavior. Naloxone, which had no effect of its own on self-stimulation, increased the dose of the analgesics required to depress response rate in a manner consistent with a competitive antagonism. In contrast, response rates were reduced at all doses of d-amphetamine tested in the presence of naloxone. Thus, the interaction between naloxone and d-amphetamine is qualitatively different from the one between naloxone and the analgesics. This finding extends to intracranial self-stimulation the generality of a previous report of interactions between d-amphetamine and naloxone on behavior in the rat.Publication No. 1303 of the Division of Basic Health Sciences of Emory University. This investigation was supported by USPHS Grant DA-00541.Recipient of Research Scientist Development Award K02-DA00008.     

Antagonism of the behavioral effects of cocaine and d-amphetamine by prazosin

Key pecking by pigeons was maintained under a 30-response fixed-ratio schedule of food delivery; lever pressing by squirrel monkeys was maintained under a 3-min fixed-interval schedule of food delivery. Administered alone, d-amphetamine (0.1–3.0 mg/kg), cocaine (1.0–3.0 mg/kg) and bupropion (1.0–30 mg/kg) either did not affect or decreased fixed-ratio responding of pigeons, whereas d-amphetamine (0.056–0.3 mg/kg) either increased or decreased (0.56 mg/kg) responding of monkeys maintained under the fixed-interval schedule. Prazosin, a selective centrally-active alpha₁ antagonist, produced a dose-dependent reversal of the rate-decreasing effects of d-amphetamine and cocaine but not of bupropion on fixed-ratio responding in pigeons. Prazosin also reversed both the rate-increasing and rate-decreasing effects of d-amphetamine on fixed-interval responding of squirrel monkeys. In contrast, the non-selective alpha-antagonist phentolamine enhanced d-amphetamine-induced decreases in fixed-ratio responding. These findings suggest that the behavioral effects of d-amphetamine and cocaine are produced at least in part by activation of central alpha₁ receptors. Prazosin may be a useful tool for better understanding the mechanisms through which cocaine, amphetamine, and other abused stimulant drugs exert their potent behavioral effects.     

Effects of scopolamine,pentobarbital, and amphetamine on radial arm maze performance in the rat

Rats were trained to obtain food pellets from the end of each arm of an eight-arm radial maze. Baseline performance was characterized by very few entries into arms from which the food pellet had already been obtained. In Experiment 1, neither d-amphetamine (0.1?3.0 mg/kg) nor pentobarbital (1.0?10.0 mg/kg) affected choice accuracy, although the rate of arm-entry increased after d-amphetamine and decreased after pentobarbital. Scopolamine (0.1?1.0 mg/kg), on the other hand, reduced both accuracy and the rate of arm entry. In a second experiment, the effects of scopolamine were replicated using a between-subjects design. Methylscopolamine (0.17, 1.0 mg/kg) was found to have little effect on performance. Multiple response criteria were also compared in the second experiment. Scopolamine was found to affect runs farther out the arm differently than it affected abbreviated arm entrances. A post-trial feeding test was also included to evaluate changes in reinforcer effectiveness, and showed that food continued to be a reinforcer after both scopolamine and methylscopolamine.