Similarities of the cataleptic state induced by beta-endorphin and morphine.

A variety of behavioral tests were used to characterize the cataleptic state induced by various treatments. Besides catalepsy, posture, locomotion, rigidity and the presence of reflexive responses were assessed. Measures of analgesia and body temperature were taken. The behavioral profiles of beta-endorphin, morphine, etonitazene, haloperidol, arecoline and GABA were compared at the time maximal catalepsy scores were obtained. Results indicated that, for an equivalent degree of catalepsy, the profile of beta-endorphin was similar to that of opiates, except for changes in body temperature; beta-endorphin's profile differed markedly from that of haloperidol, arecoline and GABA. Catalepsy was less pronounced with the latter two drugs. There were similarities in the behavioral profile of haloperidol and arecoline.

Drugs and taste aversion.

The literature on the effects of drugs on the acquisition and the magnitude of taste aversion is reviewed and discussed. Then, the results of a series of experiments on the effects of phenobarbital and related drugs on taste aversion are reported. A standard taste aversion model was used in all experiments; test drugs were injected prior to drinking in a one bottle situation on the first test day following the taste aversion treatment. Phenobarbital in doses ranging from 20 to 80 mg/kg significantly attenuated taste aversion induced by lithium chloride (LiCl) and x-radiation, the maximal effect occurred with the 60 mg/kg dose. The attenuating effect was found to be dependent upon the magnitude of the aversion to the sapid solution. Phenobarbital completely abolished aversion produced by 0.375 mEq LiCl while the attenuation effect decreased linearly with higher doses of LiCl. Results also indicate that phenobarbital's attenuating effect cannot be solely attributed to its dipsogenic characteristic or to its state dependent learning effect. Attenuation of LiCl aversion to a saccharin solution was also observed following single doses of amobarbital, 30 mg/kg, pentobarbital, 15 mg/kg, and chloropromazine, 0.75 mg/kg. Taste aversion was not affected by other doses of those drugs or by hexobarbital, barbital, and chlordiazepoxide. Phenobarbital's attenuating effect on taste aversion is discussed in relation to other known behavioral and neurophysiological effects of the drug.

Behavioral toxicity of chronic administration of fenitrothion in rats.

A battery of tests was used to assess the neurobehavioral effects of fenitrothion in doses of 10, 20 and 40 mg/kg administered daily to rats for a period of 40 days. Decreases in body weight, overt cholinergic signs, loss of many reflexes, changes in measures of motor activity and, later, indices of ataxia were observed at various times after onset of treatment with the two higher doses of fenitrothion. Mortalities occurred within 12 days in those groups but all signs of toxicity and of behavioral deficits disappeared gradually in survivors. Changes in the neurobehavioral measures were seen in only two of the animals treated with 10 mg/kg and only after more than 20 days of treatment; in one rat, weight loss, absence of some reflexes, deficits in activity and signs of ataxia preceded death by several days. Results are discussed in relation with the existing data on the behavioral toxicity of fenitrothion.

Effects of glutamate and aspartate on ataxic gait induced by 3-acetyl pyridine in rats.

The main purpose of this study was to examine the effects of intraventricular injections of glutamate and aspartate on the walking gait of rendered ataxic by the administration of 3-acetyl pyridine. Both amino acids significantly improved the walking gait of these animals. The effects of other substances known to have a stimulatory influence on locomotor activity in rats were also investigated. Amphetamine, apomorphine and thyrotropin releasing hormone (TRH) had no effect on the ataxic gait of 3-AP treated animals. Substance P significantly improved the gait of ataxic animals, but to a lesser extent than that seen with glutamate and aspartate.

The effects of various barbiturates on LiCl induced taste aversion.

The effects of various barbiturates on LiCl induced taste aversion were examined. Rats were adapted to a 23 hr and 50 min water deprivation schedule. On the Treatment Day, animals were offered a novel 0.125% saccharin solution and then administered 3.0 mEq/kg LiCl. The saccharin solution was presented again on three subsequent Test Days. Fifteen minutes prior to drinking on the first Test Day animals were injected subcutaneously with either 10, 30, and 50 mg/kg Amobarbital, 3, 9, and 15 mg/kg Pentobarbital, 40, 80, and 120 mg/kg Barbital, or 1, 3, and 9 mg/kg Hexobarbital. Results indicate that only 30 mg/kg of Amobarbital and 15 mg/kg of Pentobarbital significantly attenuated the magnitude of taste aversion.

Influence of substance P on the behavioral changes induced by haloperidol in rats.

Locomotor activity and grooming behavior of rats were recorded for a period of 30 min following intraventricular injections of substance P(SP) in doses of 0.60 and 2.50 microgram/rat. The lower dose of the peptide significantly increased locomotion for 10 min and time spent grooming for 25 min. The effects of the same two doses of SP on the hypokinesia induced by various pharmacological treatments modifying catecholaminergic systems were then examined. SP did not affect the behavioral depression produced by alpha-methyl-para-tyrosine (250 mg/kg), FLA-63 (25 mg/kg) and phenoxybenzamine (20 mg/kg). However, SP, in dose of 0.60 microgram/rat, systematically reversed the decrease in locomotor activity induced by a relatively small dose of haloperidol, 0.1 mg/kg. The dame dose of the peptide significantly counteracted the rigidity but not the hypokinesia and catalepsy resulting from the previous administration of a higher dose of haloperidol, 3 mg/kg. The results support the hypothesis that SP may exert direct or indirect function in motor behavior, possible via a modulatory action on brain dopaminergic systems.

Effects of phenobarbital on taste aversion induced by X-radiation.

The effects of phenobarbital on taste aversion induced by X-radiation were examined. Rats were adapted to a 23 hr 50 min water deprivation schedule. On the Treatment Day animals were given a novel 0.125% Na saccharin solution during the 10 min drinking session and were then exposed to 100 rads of X-radiation. The saccharin solution was presented again on six subsequent Test Days. Phenobarbital in doses of 20, 40, 60 and 80 mg/kg was administered 15 min prior to drinking on the first Test Day. Results demonstrate that phenobarbital in all doses tested has a significant attenuating effect on radiation induced taste aversion.

Effect of brain peptides on hypokinesia produced by anterolateral hypothalamic 6-OHDA lesions in rats.

Intraventricular injections of substance P, TRH and somatostatin were administered to rats rendered hypokinetic by bilateral microinjections of 6-hydroxydopamine into the anterolateral hypothalamus, Only substance P in a dose of 0.30 micrigrams/rat significantly increased motor activity as determined by photocell counts in a 5 min test session immediately after administration of the peptide. Behavioral observations indicated that grooming and not locomotion was mainly responsible for the greater activity scores. None of the three peptides at the doses examined potentiated or reduced the increased activity induced by 1 mg/kg apomorphine. Stereotyped behavior was also not affected by previous injections of substance P and somatostatin but was enhanced in animals which had received 5 micrograms/rat TRH 30 min prior to apomorphine.

Measurement of ataxia and related neurological signs in the laboratory rat.

The purpose of the present study was to design a standard battery of tests capable of quantitatively characterizing ataxia and concomitant neurological signs in the rat. In addition to a systematic analysis of the walking gait of animals, tests for activity, catalepsy, rigidity, and various reflexive responses were included in the battery. The standardization and validation of the test system was performed by determining and comparing profiles of neurobehavioral effects produced by 3-acetyl pyridine, acrylamide, pyrithiamine, and thiamine deficiency, four experimental treatments reported to induce ataxia in animals. Results indicate that profiles of neurobehavioral disturbances accompanying ataxia in animals varied distinctively with each experimental treatment.

Effects of methylphenidate on schedule dependent and schedule induced behavior.

The effects of methylphenidate, 1.5, 3.0, 6.0 and 12.0 mg/kg, on lever pressing, schedule induced licking, and drinking were studied. The generator schedule was a fixed interval 1 min food reinforcement schedule. The effects were assessed when animals were reduced to 80% body weight by partial food deprivation and when allowed to recover body weight under conditions of ad lib eating. Results indicate that under body weight conditions methylphenidate significantly decreases schedule induced licking and drinking but does not affect lever pressing.

Comparison of neurobehavioral effects induced by various experimental models of ataxia in the rat.

The purpose of the present study was to design a standard battery of tests capable of quantitatively characterizing ataxia and concomitant neurological signs in the rat. In addition to a systematic analysis of the walking gait of animals, tests for activity, catalepsy, rigidity and various reflexive responses were included in the battery. The standardization of the test system was performed by determining and comparing neurobehavioral effects produced by 3-acetyl pyridine, acrylamide, pyrithiamine and thiamine deficiency, four experimental treatments reported to induce ataxia in animals. Results indicate that profiles of neurobehavioral disturbances accompanying ataxia in animals varied distinctively with each experimental treatment.

The effects of phenobarbital on lithium chloride induced taste aversion.

The dose related effects of phenobarbital on LiCl induced taste aversion were examined. Rats were adapted to a 23 hr 50 min water deprivation schedule. On the Treatment Day animals were offered a novel 0.125% saccharin solution during the 10 min drinking session and were then administered 3.0 mEq/kg LiCl. The saccharin solution was presented again on six subsequent Test Days. Sodium phenobarbital 20, 40, 60 and 80 mg/kg was administered 15 min prior to drinking on the first Test Day. Results indicated that all doses significantly attenuated taste aversion with the maximal effect occurring with the 60 mg/kg dose.

Differential behavioral activities from anterior and posterior hypothalamic lesions in the rat.

Bilateral 6-hydroxydopamine injections into the anterolateral (AL) or posterolateral (PL) portions of the hypothalamus produced hypokinesia, catalepsy, rigidity and severe weight losses due to aphagia and adipsia. Subcutaneous administration of apomorphine, 1 mg/kg, 48 hr after 6-OHDA injections reversed temporarily the hypokinesia in both AL and PL 6-OHDA groups. However, qualitative and quantitative differences in the behavioral responses to the drug were observed. Motor activity as measured by photocell counts was significantly greater in AL 6-OHDA rats. Apomorphine induced stereotyped behavior in both groups; however, the predominant behavioral responses were oral stereotypies in PL 6-OHDA animals and sniffing in AL 6-OHDA rats.

Effects of acute and chronic administration of caffeine on schedule dependent and schedule induced behavior.

The effects of caffeine (3.125, 6.25, 12.5, 25, 50, and 100 mg/kg) on lever pressing, schedule induced licking and water consumption induced by a fixed interval 1 min schedule were studied. Changes in these dependent variables were assessed when animals were reduced to 80% of their initial body weight by partial food deprivation and when body weights recovered after the animals were returned to conditions of ad lib feeding. Results indicate differential effects of the drug between animals at 80% body weight and when they are permitted to recover. Tolerance was examined for a single large dose only for the same dependent variables in animals at 80% body weight.

Effects of phenobarbital on saccharin and citric acid intake in fluid deprived rats.

Rats were adapted to a 23 hr fluid deprivation schedule. Every third day animals were offered either 0.125 percent Na saccharin or 0.2 percent citric acid solutions in place of water during the 1 hr drinking session. Sodium phenobarbital was administered subcutaneously, 40 mg/kg, 15 min prior to drinking. Results indicate that the drug increases saccharin and citric acid consumption following the injections. No decreases in intakes of saccharin and citric acid occurred on subsequent postdrug days and the amounts of fluid consumed on these days were comparable to the baseline predrug days intakes.