Conditioned Avoidance Behavior Research Articles

Studies correlating electrically stimulated release of neurotransmitters from brain slices with conditioned avoidance behaviour modified by light reversed daytime schedules : Patel, D.R. & Turnbull, J.M., Pharmacology Department, Charing Cross & Westminster Medical School, Fulham Palace Road, London W6 8RF

Studies correlating electrically stimulated release of neurotransmitters from brain slices with conditioned avoidance behaviour modified by light reversed daytime schedules : Patel, D.R. & Turnbull, J.M., Pharmacology Department, Charing Cross & Westminster Medical School, Fulham Palace Road, London W6 8RF

Effects of centrally acting beta adrenergic agonists on discrete trial conditioned avoidance behavior in rats

The acute effects of centrally acting beta adrenergic agonists on discrete trial conditioned avoidance responding in rats were examined. Clenbuterol (0.01-3.0 mg/kg), salbutamol (0.01-30 mg/kg), and prenalterol (30-300 mg/kg) suppressed avoidance responding in a dose-dependent manner at doses that did not produce escape failures. For comparative purposes, the effects of the tricyclic antidepressant desipramine (1.0-30 mg/kg) and the antipsychotic haloperidol (0.03-0.3 mg/kg) were similarly assessed. Both compounds suppressed avoidance responding in a dose-dependent manner. Only haloperidol (0.3 mg/kg) produced escape failures. Administered alone, the beta adrenergic antagonist propranolol (1.0 and 10 mg/kg) did not affect avoidance behavior. When administered prior to clenbuterol (0.1 mg/kg), salbutamol (1.0 mg/kg), or prenalterol (100 mg/kg), propranolol antagonized the beta adrenergic agonist-induced suppression of avoidance responding. The suppressive effect of desipramine (3.0 mg/kg) on avoidance performance only tended to be attenuated by propranolol. Propranolol had no effect on the ability of haloperidol (0.1 mg/kg) to reduce avoidance responding. These results suggest that the effects of the beta adrenergic agonists clenbuterol, salbutamol, and prenalterol on discrete trial avoidance behavior are mediated, in part, through agonist interactions with beta adrenergic receptors.

Anaphylactic shock-induced conditioned taste aversion: II. Correlation between taste aversion and indicators of anaphylactic shock

Previous studies (V. J. Djurić, B. M. Marković, M. Lazarević, & B. D. Janković, 1987, in B. D. Janković, B. M. Marković, & N. H. Spector (Eds.), Neuroimmune interactions, pp. 561–568, New York: New York Acad. Sci.; B. M. Marković, V. J. Djurić, M. Lazarević, & B. D. Janković, 1988, Brain Behav. Immun. 2, 11–23) have shown that rats learn to associate the taste of saccharin with the induction of anaphylactic shock, thus exhibiting conditioned taste aversion (CTA) toward an otherwise preferred saccharin solution. The present experiment investigates the effect of unconditioned stimulus intensity (the amount of antigen used for the induction of shock) on CTA. Rats were sensitized to ovalbumin and subjected to a conditioning trial in which the conditioned stimulus (CS; saccharin solution given orally) signaled the presentation of the unconditioned stimulus (US; shocking doses of ovalbumin ranging from 0.5 to 3 mg given intraperitoneally). Behavioral signs, hematocrit, and rectal temperature were used for evaluation of anaphylactic shock. Twenty-four hours after the conditioning trial, rats were subjected to a two-bottle preference test between saccharin solution and water. Multiple regression statistical analysis revealed significant correlations among saccharin preference ratio, dose of antigen used for the induction of shock, behavioral signs of shock, rise in hematocrit, and fall in rectal temperature. A dose-dependent relation among saccharin preference ratio and physiological indicators of shock suggests that conditioned anaphylactic shock-induced avoidance behavior is functionally related to homeostatic factors involved in immune reactivity.

The propensity for schedule-induced polydipsia is related to differences in conditioned avoidance behaviour and in defense reactions in a defeat test

In line with previous research showing that animals predisposed to develop schedule-induced polydipsia when submitted to intermittent distribution of food show differential behavioural and neurochemical characteristics, the present experiments investigated the nature of defense reactions to aversive situations in rats that do or do not develop schedule-induced polydipsia. It was found that rats that engage in excessive drinking during intermittent feeding display more rapid active avoidance learning in a 2-way shuttle-box and show less freezing when confronted with an aggressive resident male in a defeat test than those that do not develop schedule-induced polydipsia. These results are consistent with the hypothesis that individual differences in the propensity to exhibit oral consummatory activities in conditions of mild stress are related to the ability to shift behavioural programmes in response to external stimulation.

Behavioral effects of quinupramine, a new tricyclic antidepressant

The effects of a new tricyclic antidepressant quinupramine (5-(3-quinuclidinyl)-10,11-dihydro-5H-dibenz [b, f] azepine) on various animal behaviors were examined in mice and rats and compared with those of imipramine, amitriptyline and maprotiline. Quinupramine antagonized haloperidol-induced catalepsy and tetrabenazine-induced ptosis and potentiated methamphetamine- and apomorphine-induced stereotyped behavior. These effects were almost the same as or even more potent than those of imipramine and amitriptyline. Quinupramine decreased locomotor activity in mice, but potentiated methamphetamine-induced hyperactivity to a greater degree than imipramine and amitriptyline. On the other hand, quinupramine inhibited muricide in accumbens-lesioned rats, but did not prominently inhibit muricide in olfactory-bulbectomized and raphe-lesioned rats. Quinupramine decreased the duration of immobility in low doses without affecting locomotor activity, and this effect was almost the same as that of imipramine and amitriptyline and more potent than that of maprotiline. Quinupramine antagonized physostigmine lethality and oxotremorine-induced tremor, suggesting that quinupramine has a central anticholinergic action. Quinupramine, like imipramine and amitriptyline, has no effect on conditioned avoidance behavior. In conclusion, quinupramine generally has the same behavioral profile as typical tricyclic antidepressants, but it has somewhat different effects from imipramine and amitriptyline since quinupramine has a potent central anticholinergic and a weak antimuricide effect.

Participation of the nigro-striatal and mesolimbic dopaminergic systems of the brain in the control of components of learned motor responses in dogs

We studied the role of the striatal and limbic dopaminergic systems in the regulation of instrumentally conditioned avoidance behavior and postural adjustment in chronic experiments on dogs. Dopamine in doses of 3 micrograms was introduced bilaterally into the caudate nucleus head and the nucleus accumbens of the forebrain through implanted cannuli. Predominantly unidirectional effects were demonstrated, but a clear acceleration of the initiations of both conditioned-reflex postural adjustment and voluntary movement were obtained from the caudate nucleus; there was a marked degree of expressiveness to this movement. The greatest effects were obtained during simultaneous, bilateral introduction of dopamine into both structures in dogs with an akinetic form of motor pathology. We conclude that the integration of the striatal and limbic dopaminergic systems is of critical necessity for the initiation and regulation of the components of voluntary movement.

Repeated testing of rats markedly enhances the duration of effects induced by haloperidol on treadmill locomotion, catalepsy, and a conditioned avoidance response

In the present experiments we have investigated the duration of haloperidol-induced effects in rats tested repeatedly, and in rats tested on a single occasion after drug administration. The behavioral test situations used include treadmill locomotion (speed 4 m/min), inclined grid catalepsy, two-way conditioned avoidance behavior and open field spontaneous locomotor activity. It was found that the duration of haloperidol-induced effects on treadmill locomotion, spontaneous locomotor activity, catalepsy and a conditioned avoidance response (doses: 0.32, 0.32, 1.25 and 0.2 mg/kg IP, respectively) was about 2 hr or less in animals observed once only (“independent procedure”). With the possible exception for locomotor activity, the duration of haloperidol-induced effects was considerably prolonged, up to 8 hr depending on the test situation, in animals observed repeatedly after the administration of haloperidol in the same doses (“dependent procedure”). The enhanced duration by the dependent procedure is probably not caused by handling stress since the enhanced duration of haloperidol-induced effects in some of the behavioral tests were only noted in animals tested repeatedly in one particular test, and not in animals given the repeated pretests in another situation. Furthermore, it was not possible to relate the enhanced duration of haloperidol-induced effects by repeated testing to changes in striatal DA metabolism as evaluated by measurements of DOPAC, HVA and DA. It was found that the treadmill test 2–4 hr after haloperidol (0.12–0.32 mg/kg IP), at certain doses and time intervals produced an increase in DA turnover [(DOPAC + HVA)/DA], but this increase was the same in both procedures (dependent and independent). Our findings that the time-course of action of haloperidol is dependent on the test procedures used may be of importance when interpreting interaction studies and the relationship between pharmacokinetics and behavioral effects of this, and possible other, psychotropic drugs.

A tripeptide protease inhibitor attenuates conditioned avoidance behavior

In a single 10-s training trial, hatchling chicks were conditioned to suppress their spontaneous peck response to a small spherical target by coating it with an aversive liquid. A 24-h test trial employing a dry target demonstrated a robust memory for the training manifested in passive avoidance behavior. Leupeptin, a low-molecular-weight antiprotease, injected i.c.v. 1 h or 15 min prior to training attenuated the long-term avoidance response but not the initial training-induced peck suppression. Leupeptin had no effect on memory if given posttraining. A dose response experiment revealed that a 100- or 200-μg dose of leupeptin reliably impaired conditioned avoidance, whereas a 25 or 50-μg dose was ineffective. A dipeptide leupeptin analog ( l-leucyl- l-arginine) possessed one-half the potency of the tripeptide in the memory task, and a different protease inhibitor (aprotinin) failed to effect the conditioned avoidance behavior. The mechanisms by which leupeptin may exert its influence in this behavioral paradigm and others are discussed.

Neurobehavioral effects of the calcium ionophore A23187

The divalent cationic ionophore A23187 (calimycin) facilitates the transport of calcium ions across biological membranes, resulting in an increase of cytosolic calcium. A23187 has been used extensively in vitro to activate calcium-dependent neurocellular processes. Because of its potential usefulness as a neurotoxicological probe, our laboratory conducted a series of studies to characterize the neurofunctional consequences of A23187 in the intact organism. In addition to approximating the LD50, the effects of acute parenteral administration of A23187 on conditioned avoidance, nociceptive shock threshold, open-field activity, consummatory behavior, body temperature and neuromotor function, including general activity, coordination, balance and grip strength, were assessed in the rodent. The LD50 of A23187, administered intraperitoneally to adult male rats, was 9.2 mg/kg. The predominant overt signs of toxicity included lethargy, limb weakness and apnea. Lower doses, from 0.5 to 0.03 mg/kg, produced a variety of more subtle neurobehavioral effects, including a selective depression of motor activity, a moderate elevation of shock threshold, altered conditioned avoidance behavior and hypothermia.

Chapter 10 Neurohypophyseal hormones and behavior

This chapter reviews the roles of the neurohypophyseal neuropeptides in drug and ethanol addiction, and in learning and memory processes. Among a wide variety of neuropeptides, vasopressin (VP) [arginine-vasopressin (AVP)] and oxytocin (OXT) play important roles in various functions of the central nervous system, including learning and memory processes, regulation of cardiovascular functions, adaptive mechanisms of drug addiction, and tolerance to ethanol. The morphological and functional basis of the fundamental role of these peptides is their presence in the cerebrospinal fluid and in nerve fibers and terminals of various extrahypothalamic brain regions. Synaptically stored AVP and OXT can be released from the nerve terminals by various stimuli that cause neuronal depolarization. The neurohypophyseal neuropeptides also modulate the activity of non-peptidergic neuronal transmission. Thus, it is likely that the neurohypophyseal neuropeptides may act likewise as neuromodulators (regulators) in the central nervous system. The neuropeptides of the posterior pituitary have profound effects on behavioral processes in laboratory animals. Powerful peptide effects are observed on adaptive central nervous mechanisms involved in drug and ethanol addiction and in conditioned avoidance behavior.

Long-term effects of early status epilepticus on the acquisition of conditioned avoidance behavior in rats.

The acquisition of active avoidance behavior in a shuttle-box apparatus was studied in 45-day-old rats. In these animals a single episode of status epilepticus had been induced by the systemic administration of kainic acid (KA) or pentylenetetrazole (PTZ), when they were 10 or 25 days old. The results were compared with those obtained from animals in which, at the same ages, only saline solution had been injected. In KA-treated rats a decrement of right responses and a prolonged reaction time were observed, with these results more evident in animals treated earlier (10 days). Parallel with the behavioral alterations, the histological, morphometric and morphological examinations revealed neuronal and glial abnormalities at the neocortical level, while no lesions were found in the hippocampus. PTZ-treated rats showed no behavioral alteration nor histological abnormality. The different findings obtained after KA and PTZ injection suggest that not only status epilepticus per se, but the mechanism of action and the neurotoxicity of the convulsant agent, are very important in impairing late performances.

Leu-enkephalin actions on avoidance conditioning are mediated by a peripheral opioid mechanism

Leu-enkephalin (100 ug/kg, i.p.) administered to mice 5 min before training in a one way active avoidance task significantly reduced the number of avoidance observed in the peptide treated animals. This impairing action of Leu-enkephalin was partially attenuated by methylnaloxonium (naloxonium), a quarternary form of naloxone with a limited ability to penetrate the blood brain barrier. Passive immunization (i.v.) of mice with a Leu-enkephalin antiserum 4 hrs before training produced an effect on avoidance conditioning that was the opposite to that observed with Leu-enkephalin alone. That is, passive immunization increased the number of avoidances observed in the treated mice. The results suggest that Leu-enkephalin actions on avoidance conditioning are mediated by a peripheral opioid mechanism, that leu-enkephalin may have a primary site of action outside the blood brain barrier, and that peripheral Leu-enkephalin systems may normally operate to influence conditioned avoidance behavior.

Plasma prolactin levels during conditioned avoidance behavior in rats

In these experiments, we examined the prolactin (PRL) response during the acquisition of a conditioned avoidance response (CAR). Rats were tested daily in a two-way shuttle box. They were presented with a light stimulation followed by an electric footshock. During each trial period, the rats were given the opportunity to escape the footshock by moving to a safe side of the box. Movement to the appropriate location after the warning signal (light) begins, but before the onset of the footshock, constitutes a CAR. Blood samples were collected from an indwelling cannula and analyzed by radioimmunoassay. PRL levels increased during early acquisition testing, when the rats had not learned to avoid the shock. After one week of testing, acquisition performance increased considerably (70% CARs) while PRL levels remained unchanged. Thus, we were able to show that as rats learned to modify their behavior in response to a stressful situation, they could also modify their PRL response to the stressor.

The acute effects of antidepressant drugs on the performance of conditioned avoidance behavior in rats

The effects of acute administration of 10 different antidepressant drugs were examined on the performance of a two-way conditioned avoidance response in rats. The antidepressant drugs impaired avoidance behavior by decreasing avoidance responding and increasing the number of escape failures. The order of effectiveness for increasing overall response latency at a common dose of 10 mg/kg was: desipramine, maprotiline, protriptyline, (+) oxaprotiline, nortriptyline, imipramine, amtiriptyline, (−) oxaprotiline, fluoxetine, and chlorimipramine. Avoidance behavior was impaired most by those antidepressant drugs that are also potent inhibitors of norepinephrine uptake.

Brain dopamine and noradrenaline concentrations in reference to acquisition of conditioned avoidance behaviour in intact and orchectomized rats.

Brain dopamine and noradrenaline concentrations in reference to acquisition of conditioned avoidance behaviour in intact and orchectomized rats.

Arginine vasotocin delays extinction of a conditioned avoidance behavior in neonatal chicks

One minute after single-trial avoidance conditioning, young cockerels received intracerebroventricular or intraperitoneal injections of saline or arginine vasotocin (dose range: 0.004 to 16 μg/chick). Retroactive enhancement of the learned response was observed 24 hours post-training for some dose levels, but not for others. A 0.4 μg vasotocin dose also delayed extinction when injected 9 minutes after training. Behavioral similarities between avian and mammalian responses to vasotocin and other neuroactive peptides are discussed.

Conditioned lever-press avoidance response in mice: acquisition processes and effects of diazepam.

Acquisition of conditioned lever-press avoidance behavior on a continuous avoidance schedule (response-shock interval = 30 s and shock-shock interval = 5 s) and on a discrete avoidance schedule (intertrial interval = 25 s and duration of the warning presentation = 5 s with an escape contingency) in dd mice was investigated. When the behavioral baseline had stabilized, the effects of diazepam on avoidance behaviors were examined. About 60% and 80% of the mice achieved criterion levels of avoidance behavior under continuous avoidance (shock rate being less than 0.5/min) and discrete avoidance (avoidance rate being higher than 75%), respectively. Diazepam (0.5--4 mg/kg SC) dose-dependently impaired avoidance behavior of mice which had a low baseline shock rate and a high baseline avoidance rate under continuous and discrete avoidances, respectively. The changes in avoidance behavior in mice after diazepam were almost identical with those previously found in rats.

Anterior thalamic lesions and neuronal activity in the cingulate and retrosplenial cortices during discriminative avoidance behavior in rabbits.

Bilateral electrolytic lesions of the anteroventral (AV) nucleus of the thalamus given after training impaired retention performance (extinction and reacquisition) of rabbits in a differential avoidance conditioning task. In addition, the lesions abolished the excitatory, discriminative multiple-unit discharges that had developed in the cingulate and retrosplenial cortices to the auditory conditional stimuli (CSs) during the course of behavioral acquisition, prior to the induction of the lesions. The excitatory discharges were supplanted in the subjects with lesions by CS-elicited reduction of neuronal firing to levels below the prestimulus baseline. Lesions given before training did not disrupt behavioral acquisition, but they did eliminate the excitatory tone-elicited neuronal discharges that normally occur in the cortex before and during training. The CS-elicited reduction of neuronal firing did not occur at the beginning of training in the subjects given lesions before training, but it developed during the course of training. The lesions did not eliminate the excitatory and discriminative neuronal activity of the prefrontal cortex. These results demonstrate that excitatory and discriminative neuronal discharges in the cingulate and retrosplenial cortices are critically dependent on the connections of these areas with the anterior thalamic nuclei. Also the lesion-induced disruption of performance during extinction and reacquisition but not during original learning confirms a prediction from past electrophysiological studies, that the AV thalamic nucleus is involved in the mediation of the maintenance and retention of the conditioned avoidance behavior, but not in its original acquisition.

Tolerance to the anti-avoidance properties of cholecystokinin-octapeptide

Previous investigations have suggested a neuroleptic-like action of cholecystokinin-octapeptide (CCK8) on conditioned-avoidance behavior. This study was initiated to test tolerance to this effect. Rats were trained to avoid electric shock in a shuttle box under a free-operant (Sidman) avoidance paradigm. Each shuttle response postponed a 0.2 sec, 1 mA shock for 20 sec. If the rat failed to respond, shock was delivered every 5 sec until a response occurred. After avoidance training, half of the rats received two daily injections of CCK8 (0.320 mg/kg, IP) and half received saline for 7 days. Rats were then tested on the Sidman avoidance 1 min after receiving CCK8 (0.640 mg/kg, IP) or saline. CCK8 depressed avoidance responding if rats received saline for 7 days prior to the test. Rats pretreated with CCK8 for 7 days were not significantly affected by CCK8 during the avoidance test. Thus, repeated injections of CCK8 result in tolerance to its anti-avoidance properties.

Drug induced supersensitivity as measured by electrical self-stimulation and conditioned avoidance behavior

Drug induced supersensitivity as measured by electrical self-stimulation and conditioned avoidance behavior