Effects of chlordiazepoxide and pentobarbital on conflict behavior in rats

A punishment discrimination (conflict) was conditioned in rats by simultaneously rewarding with food (sweetened, condensed milk) and punishing with shock all lever responses made in the presence of an auditory stimulus. Chlordiazepoxide and pentobarbital were administered in order to compare degrees of attenuation of conflict behavior relative to the production of behavioral debilitation. Chlordiazepoxide produced the maximum attenuation at doses that produced only minimum debilitation. In general, conflict attenuation (anti-anxiety) was greater under chlordiazepoxide while general debilitation (behavioral toxicity) was greater for pentobarbital.     

Effects of chlordiazepoxide upon differential heart rate conditioning in rats

Chlordiazepoxide (CDP) at 20 mg/kg, i.p. almost completely blocked classical differential conditioning in heart rate (HR) in unanesthetized rats. But it only slightly, if any, despressed simple HR conditioning to the same conditioned stimulus (CS). The simultaneously observed differential conditioning in respiratory rate (RR) was also inhibited by CDP with its little effect upon simple RR conditioning. Motor activity as measured by changes in EMG records immediately preceding as well as during the CS was not affected either by CDP or by the differential conditioning procedure. Results were explained in terms of the drug's disinhibitory action.     

Effects of d-amphetamine and chlordiazepoxide on positive conditioned suppression

Six rats lever-pressed under a variable-interval 80-sec food reinforcement schedule. After responding had stabilized, an 8-sec tone terminating with food delivery was superimposed on the variable-interval schedule on the average once every five minutes without regard to the animal's behavior. This positive conditioned suppression procedure consistently reduced responding during the pre-food stimulus (tone). Neither d-amphetamine (0.5, 1.0, 2.0 mg/kg) nor chlordiazepoxide (7.5, 15, 30 mg/kg) significantly affected the relative suppression produced by the tone. Instead, both drugs produced generally non-selective effects, similarly affecting response rate in the presence and absence of the tone.     

Effects of isoproterenol and chlordiazepoxide on drinking and conflict behaviors in rats

Isoproterenol, a beta-adrenergic agent, induced drinking in water-satiated rats. Isoproterenol exhibited significant anti-conflict activity in water-deprived rats in the Shock-induced Suppression of Drinking (SSD) procedure. Chlordiazepoxide (CDP), at the highest dose tested, also increased drinking in non-deprived naive rats. As expected, CDP demonstrated highly significant anti-conflict activity in thirsty rats (SSD test). These results suggest that in conflict procedures, where food or water is used as a reward, agents that affect the consumatory drive mechanisms could show up as “false positives.” Moreover, agents that affect primary drives (e.g., CDP), in addition to their anti-anxiety activity, could show additive activity in such conflict procedures.     

Effects of chlordiazepoxide on maze performance of rats subjected to undernutrition in early life

The purpose of this research was to study the isolated effects of and interactions between undernutrition and emotional reactivity upon maze performance in rats. This work compares the effects of chlordiazepoxide on learning performance in two groups of adults rats: one undernourished early in life and then rehabilitated, and the other normally nourished. Chlordiazepoxide was used at 5 mg/kg body weight administered i.p. 30 min before each test. The response was evaluated in a Hebb-Williams maze. Water was used as reinforcement. Chlordiazepoxide improved performance in the early undernourished group 197±55.9 errors to 149±33.6 (mean±SD). Chlordiazepoxide impaired performance of the normal group from 107±22.7 errors to 197±42.2 errors. Analysis of variance gave an F=6.64, which is significant (P<0.01). This supports the hypothesis that the high emotional level of previously undernourished subjects acts negatively upon problem-solving performance.This work was in partial fulfilment of the requirements for the degree of Master of Science in Human Nutrition     

Effects of chlordiazepoxide on discriminative fear conditioning and shuttle avoidance performance in the rabbit

Previously acquired shuttle avoidance performance in rabbits was reduced by chlordiazepoxide. Other animals were given chlordiazepoxide during differential tone-shock pairings. The effects of this differential Pavlovian fear conditioning were tested during extinction, when the tonal CSs were imposed upon the signal for the previously acquired shuttle avoidance response. Comparison with saline controls showed that chlordiazepoxide did not disrupt fear conditioning. It is also suggested that the decrement produced by chlordiazepoxide was not due to a sensory or motor impairment.     

Effects of chlordiazepoxide and flumazenil on preference for punished and unpunished response alternatives in rats

Male food-restricted hooded rats were trained to respond on a two-component multiple schedule. Reinforcement density was several times higher in one component than in the other. However, responses were intermittently punished with shock in the richer reinforcement component (conflict situation). Shock intensities were adjusted to produce mild and strong suppression of responding in two separate phases. Half of the rats controlled which component was operating (Preference group) and half did not (Yoked group). The effect of chlordiazepoxide (CDZ; 0, 1, 3, and 10 mg/kg; IP) was measured on component preference and response rate. Chlordiazepoxide increased both time spent in the conflict situation and response rate in that component. This is the first study employing a schedule that permitted these two behavioral indices to be measured independently in a conflict paradigm. Response rates were also increased in the unpunished response alternative, but to a lesser degree than in the conflict situation. The effects of CDZ were at least partially mediated by the benzodiazepine receptor because CDZ's effects were diminished by flumanezil (10 mg/kg; IP), a benzodiazepine antagonist.     

The mechanism of fixation prevention and “Dissociation” learning with chlordiazepoxide

Summary This experiment investigated the possibility that chlordiazepoxide (CDP) has unique properties that account for state dependent learning, and prevention of conflict-induced behavior fixations.One group of rats were given a discrimination problem on a Lashley jumping stand, but on even days all responses were punished. Another group were treated the same way except than on even days all responses were rewarded. Each of these groups were subdivided, half of the Ss were given CDP on even days, the other half no drug. The results showed that punishment on even days for the response to be learned disrupted learning more than reward for responses that were to be avoided. CDP practically eliminated these disruptive effects and aided learning for the punishment group, but led to a slower rate of learning for the reward group. These findings confirmed the hypothesis that CDP attenuates the effects of negative incentives, and that this property accounts for the drug's cue value in discrimination learning and for its fixation prevention characteristics.This experiment was supported by Research Grant MH-01061, United States Public Health Service. Chlordiazepoxide was generously supplied by HoffmannLaRoche Inc., Nutley, New Jersey. The animals were run by Pieper Toyama and Nancy F. Feldman. The statistical analysis was done by Dennison Smith. Nancy F. Feldman also composed and drew the figures.     

Aversive conditioning by psychoactive drugs: Effects of morphine,alcohol and chlordiazepoxide

Some investigators have used evidence that a drug may induce conditioned taste aversion to dismiss other behavioral effects of the drug as due to general toxicity rather than specific pharmacological action. To test the validity of this position, behaviorally relevant doses of alcohol, chlordiazepoxide, and morphine were studied in an aversive taste conditioning paradigm. Drug injections were paired with exposure to saccharin solution on repeated trials. Each drug produced saccharin aversion at one or more doses. Since comparable doses are known to facilitate rather than impair behavior in some situations, the taste aversion test is insufficient to establish the general behavioral toxicity of particular drug doses.     

Propranolol and chlordiazepoxide on experimentally induced conflict and shuttle box performance in rodents

Propranolol failed to attenuate the suppression of behavior caused by experimentally induced conflict in rats and failed to enhance the avoidance performance of partially trained mice in a shuttle-box situation, effects which are observed after chlordiazepoxide. When given in combination with chlordiazepoxide, propranolol did not influence the effects of the tranquilizer in either procedure.     

Effects of intracerebroventricular injection of naloxone on operant feeding and drinking in pigs

Operant feeding and drinking to satiation were studied in prepubertal pigs deprived of food or water for 18 hours and then given intracerebroventricular (ICV) injections of a solution of naloxone hydrochloride. In feeding tests there was no difference in the amount of food consumed, or in the rate at which reinforcements were obtained, between pigs given ICV injections of 0.4 or 0.8 mg naloxone and those receiving a control injection of saline. However, in drinking tests, injection of both 0.2 and 0.4 mg naloxone significantly (p less than 0.01) reduced the quantity of water drunk and slowed the rate at which reinforcements were obtained. No significant effects on operant water intake were seen after intravenous injection of 0.4 mg naloxone.     

Behavioural and pharmacological dissociation of chlordiazepoxide effects on discrimination and punished responding

Effects of chlordiazepoxide (CDP) and ethanolamine-O-sulphate (EOS) alone and in combination were tested on the acquisition and performance of continuous reinforcement — time out (CR-TO) and variable interval reinforcement — time out (VI-TO) operant discriminations in rats. CDP disrupted acquisition of CR-TO discrimination; effects were short lived, and neither CR-TO performance nor its reversal were impaired. Acquisition of VI-TO discrimination was increasingly impaired, and performance disrupted in pre-trained animals. EOS alone was inactive, and with CDP exerted only slight interactive effects. When a conflict component was added to the VI-TO schedule, however, EOS showed substantial additive effects with CDP on punished responding.The results suggest that CDP-induced increases in non-rewarded (TO) responding were related to task difficulty, pointing to a discrimination impairment rather than an anxiolytic effect. In addition, the specificity of EOS potentiation may reflect a pharmacological dissociation between CDP effects on discrimination and on punished responding, and suggest that GABA is selectively involved in resistance to punishment.This work was in part supported by the award of MRC project Grant No. 8313090N to SG     

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.     

Changes in the amnesic and aversive properties of avoidance conditioning with chlordiazepoxide

In two series of experiments the effects were investigated of chlordiazepoxide (CDP) upon acquisition of avoidance behavior in mice using footshock to establish an avoidance response and posttrial electroconvulsive shock (ECS) to retroactively disrupt the retention of that response. The relationship of either footshock and/or ECS during passive avoidance conditioning acquisition following prior drug treatment provided for reduced active avoidance response acquisition where such training was given following assessment of the retention of the passive avoidance behavior. The present experiments suggest that chlordiazepoxide interacts with acquired avoidance behavior such as to modify the amnesic properties of ECS. This may be due to a partial antagonism of the ECS induced retrograde amnesia, or to modification of active avoidance acquisition by drug treatment.     

Effects of chlordiazepoxide on tail pinch-induced eating in rats

The effects of 5, 10, and 20 mg/kg chlordiazepoxide on tail pinch (TP)-induced behavior were investigated. Five mg/kg enhanced TP-induced eating in terms of both latency and duration. Twenty mg/kg had decremental effects. All doses of the drug reduced the incidence of clip-directed behavior, but increased locomotor activity during the TP trials in a dose-dependent manner. On control trials, the drug increased locomotor activity at the low dose and eating at the high dose. The results are examined in terms of the various behavioral actions of the minor tranquilizers. The implications for the behavioral and neuropharmacological mechanisms underlying TP-induced and other forms of stimulus-bound behavior are discussed.     

Effects of septal lesions and chlordiazepoxide (Librium) on avoidance behavior in rats

The combined effects of septal lesions and chlordiazepoxide (CDP) were observed during 5 consecutive procedures involving active avoidance, and passive avoidance during approach-avoidance conflict. The Maier paradigm on a Lashley jumpingapparatus was used. The studies led to the following results and conclusions. Septal lesions had no effect on response latency in an active avoidance test. Septal lesions reduced latencies during conflict and learning tests when negative incentives were salient features. Adding CDP reduced latencies further. During extinction tests when negative incentives were withdrawn, response latency for the controls declined to that of the septal-lesioned rats. (Thus, the disinhibitory effects of septal-lesioned rats.) Thus, the disinhibitory effects of septal lesions that become manifest during passive avoidance tests, are enhanced by CDP. This suggests that the septum is not a significant site for CDP action.     

Dimensions of the LSD,methylphenidate and chlordiazepoxide experiences

Summary Through the retrospective use of the 156 item DWM Card Sort, the experiences from a single intravenous dose of 200 mcg of LSD, 75 mg of methylphenidate (Ritalin) and 75 mg of chlordiazepoxide (Librium) were compared in a population of 99 chronic male alcoholics treated in an LSD setting in a double-blind study. Surprisingly, 96 of the 156 items proved significantly different among the 3 groups. LSD was unique in producing Sensory and Perceptual Distortions (including Hallucinations or Illusions), and Mystical, Religious or Paranormal Sensations. However, contrary to expectation, LSD did not uniquely produce the traditional therapeutic experience, but appeared to be surpassed in that area by methylphenidate. Both drugs also produced some anxiety, while chlordiazepoxide produced relaxation, and enhanced music appreciation.This investigation was supported by PHS Research Grant No. MH-11272 from the National Institute of Mental Health and the Vista Hill Psychiatric Foundation, San Diego, California. Further assistance was given by the Alcoholism Research Clinic, Department of Psychiatry, U.C.L.A. Center for the Health Sciences, Los Angeles, California. Computations were done at the Health Sciences Computing Facility under N.I.H. Grant No. FR-3. The authors are also indebted to the Scientific Advisory Council of the Licensed Beverage Industries, California; and to the San Diego County Department of Honor Camps. We also wish to extend great thanks to Mr. James C. Reed, Jr., Director of the Department of Honor Camps. In addition we wish to express our gratitude to the Staff at the Viejas Treatment Center, and to the Mesa Vista Hospital Volunteer Aides; without their continued enthusiasm and cooperation, this project would not have been possible.An Appendix has been submitted for publication to the American Documentation Institute, a Section of the Library of Congress.     

Effects of repeated administration of chlordiazepoxide on spontaneous locomotor activity in mice

Spontaneous locomotor activity has been studied in mice treated with single or repeated doses (five daily injections) of chlordiazepoxide. The repeated administration enhanced the stimulatory action of the lower doses of the drug, while the depressant effect of the higher doses was reduced.     

The effects of chlordiazepoxide HCl administration upon punishment and conditioned suppression in the rat

Rats were trained to lever press for sucrose on a random interval (RI) 64-s schedule. During a 55 min session there were four 3 min intrusion periods signalled by a flashing house-light. In experiment 1 there were two groups matched for baseline response rate. During the intrusion periods one group received response-independent footshock on an independent RI64 schedule; the other group received responsecontingent shock on this schedule. Shock intensity was varied for each rat to match degree of response suppression between the two groups. Chlordiazepoxide HCl (CDP) in doses 0.5–5 mg/kg alleviated response suppression equally in both groups. Experiment II followed the same procedure, except that all animals had the same shock intensity, producing greater response suppression in the response-contingent shock groups. CDP alleviated response suppression more in the response-contingent shock groups, significantly so at 5 mg/kg, nonsignificantly at 1 mg/kg. These results suggest that previous reports that CDP differentially alleviates the response suppression produced by response-contingent shock are an artefact of rate dependency.