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PubMed2000

Cerebellar posterior interpositus nucleus as an enhancer of classically conditioned eyelid responses in alert cats.

Cerebellar posterior interpositus neurons were recorded in cats during delayed and trace conditioning of eyeblinks. Type A neurons increased their firing in the time interval between conditioned and unconditioned stimulus presentations for both paradigms, while type B neurons decreased it. The discharge of different type A neurons recorded across successive conditioning sessions increased, with slopes of 0.061-0.078 spikes/s/trial. Both types of neurons modified their firing several trials in advance of the appearance of eyelid conditioned responses, but for each conditioned stimulus presentation their response started after conditioned response onset. Interpositus microstimulation evoked eyelid responses similar in amplitude and profiles to conditioned responses, and microinjection of muscimol decreased conditioned response amplitude. It is proposed that the interpositus nucleus is an enhancer, but not the initiator, of eyelid conditioned responses.

Action Potentials↗
PubMed1999

Conditioned effects produced by naltrexone doses that reduce ethanol-reinforced responding in rhesus monkeys.

Clinical trials have shown that naltrexone is effective in treating alcohol dependence; nausea and dysphoria have been reported as "side effects" in many of these studies. In primates, naltrexone reduces reinforced responding for oral ethanol, sucrose, and phencyclidine. This study was designed to determine if naltrexone reduces reinforced responding for various solutions by producing an interoceptive stimulus that may result in a conditioned taste aversion. Four opioid antagonist-naive rhesus monkeys responded for solutions from a two-spout operant panel for 30 min per day. During a conditioning phase, the monkeys received novel Kool-Aid solutions paired with either saline or naltrexone (0.32 mg/kg) given 30 min before the session. The monkeys then had seven choice sessions between the saline-paired solution or the naltrexone-paired solution. During the conditioning phase, the naltrexone reduced responding after five naltrexone/solution pairings. In addition, a conditioned taste aversion was produced; the naltrexone-paired solution maintained significantly less responding than did the saline-paired solution during the choice phase. In the next phase, the saline and naltrexone were given "unpaired" from any distinct part of the operant session, and another seven choice sessions followed. Naltrexone had no effect when given "unpaired" from the operant session. Then, another conditioning phase was undertaken followed by another series of choice sessions. During the replication of the conditioning, naltrexone reduced responding by the second pairing, although no conditioned aversion was observed in the subsequent choice sessions. Thus, given in the same manner (dose, route, and pretreatment time) as situations in which naltrexone reduces oral ethanol-, sucrose-, and phencyclidine-reinforced responding, naltrexone produced a conditioned taste aversion. These results suggest that naltrexone-induced nausea and its conditioned effects should be considered in naltrexone's effect in alcoholics.

Alcohol Drinking↗
PubMedDate not supplied

[Activity of neurons in the pedunculopontine nucleus in conditioned instrumental appetitive reflex].

Activity of 91 neurons in the compact and diffuse parts of the pedunculopontine tegmental nucleus (PPTg) was recorded in freely moving rabbits during execution of instrumental appetitive conditioning. Of the recorded neurons, 37.4% changed their activity in response to a conditioned stimulus, which is the evidence for the PPTg involvement in instrumental conditioning. Excitatory conditioned neuronal responses to the conditioned stimulus and food reinforcement significantly prevailed over inhibitory reactions. Neuronal responses to the conditioned stimulus were classified in several basic patterns reflecting stimulus effects, structure of the behavioral act, and reinforcement properties. These reactions indicate the involvement of the PPTg in attention, motor learning, and reinforcement. The revealed differences in associative reactive properties of the compact and diffuse parts of the PPTg to the conditioned stimulus and reinforcement point to the functional heterogeneity of this structure and suggest the leading role of the cholinergic part of the PPTg in instrumental appetitive conditioning and reinforcement as well as the essential contribution of the diffuse part into classical appetitive conditioning.

Animals↗
PubMed2004

Effects of complete immunotoxin lesions of the cholinergic basal forebrain on fear conditioning and spatial learning.

Administration of muscarinic cholinergic antagonists such as scopolamine impairs the acquisition of contextual fear conditioning, but the role of the basal forebrain (BF) cholinergic system in consolidation is unclear. To test the hypothesis that BF cholinergic neurons are critical for acquisition and consolidation of fear conditioning, male Sprague-Dawley rats with 192 IgG-saporin lesions of the entire cholinergic BF made either before or after fear conditioning were tested for conditioned fear to context and tone by assessing freezing and 22 kHz ultrasonic vocalization (USV) responses. Spatial learning in a 1-day water maze task provided a comparison for effects of the BF lesions on fear conditioning. In the test phase, neither pre-training nor posttraining BF lesions affected freezing to the context or tone. During both training and testing, pre-lesioned rats were impaired in production of USVs associated with fear. Postlesioned rats emitted fewer USVs only during testing. Acquisition of a spatial water maze task was mildly impaired in lesioned rats, although probe trial and cued performance was unimpaired. Nevertheless, these data suggest that conditioned fear-induced USVs are more sensitive to the loss of BF cholinergic neurons than is conditioned fear-induced freezing. The failure of BF cholinergic lesions to impair contextual fear conditioning indicates that scopolamine-induced impairments in fear conditioning may not be mediated by affecting cholinergic input to the hippocampus and neocortex.

Animals↗
PubMed1994

Development of IVM-IVF produced 8-cell bovine embryos in simple, serum-free media after conditioning or co-culture with buffalo rat liver cells.

Development of 8-cell bovine embryos derived from in vitro matured/in vitro fertilized (IVM/IVF) oocytes was evaluated in two simple, serum-free media (CZB and SOM) with buffalo rat liver cells co-culture (BRLC) or after conditioning compared to a commonly used, serum-supplemented complex medium TCM-199. In a 3 x 4 factorial design, 578 eight-cell embryos were randomly assigned to 12 treatment groups. The factors were: first, type of culture medium (M199/FBS, CZBg and SOM), and second, the use of BRLC (as co-culture or to condition media for 24 hr and 48 hr) and unconditioned media. Development to morula was not affected by the type of medium, but co-culture and 48 hr conditioning within media type resulted in better development when compared to the 24-hr conditioned or unconditioned groups. Blastocyst development in SOM (38.9%) was different (P < 0.05) than in CZBg (46.6%) and M199/FBS (48.7%) and was lowest in the unconditioned group (27.8%) followed by 24 hr conditioned (33.3%), 48 hr (56.3%), and co-culture (59.6%). No blastocyst expansion was observed with unconditioned media and 24 hr conditioned SOM. Significant differences (P < 0.05) were found among all treatment groups except the co-culture and 48-hr conditioned groups. Hatching occurred only with co-culture and 48-hr conditioned groups of M199/FBS and CZBg media. These data show that CZB with glucose conditioned by BRLC monolayers for 48 hr can support the development of IVM/IVF produced bovine embryos to blastocyst compared to culture in TCM-199 with serum.

Animals↗
PubMed1986

Differential Pavlovian conditioning in the mollusc Pleurobranchaea.

The present differential Pavlovian conditioning experiments on the sea slug Pleurobranchaea californica extend conditioning described in a preceding paper and provide the conditioning foundation for studies reported in another accompanying paper comparing learned behavior in whole animals with the behavior and motor patterns of electrophysiological preparations. All animals received two appetitive-conditioned stimuli (CSs), one derived from beer (Sbr) and the other derived from squid muscle (Ssq), in different temporal relationships to an electric shock unconditioned stimulus (UCS). Two groups of animals were run concurrently. One group (n = 19) received Sbr as the CS+ in close temporal pairing with the UCS, and Ssq as the CS- explicitly unpaired with the UCS (Sbr +/Ssq-). The second group (n = 20) received the opposite contingencies (Sbr-/Ssq+). All animals received only one day of conditioning involving 5 trials with an intertrial interval of 2 h. There were two replicate experiments, each involving about half of the total n, and each yielding similar results as the sum we report here. Before conditioning, animals exhibited feeding behavior (extension of the proboscis and bite-strike responses) to both stimuli at similar low thresholds. Conditioning produced long-term behavioral changes in all animals throughout the 4.5-day postconditioning observation period. However, only the Sbr+/Ssq- animals consistently exhibited the appropriate differentially conditioned food-aversion behavior which consisted of strong withdrawal and high-threshold feeding responses to Sbr, and low-threshold feeding responses to Ssq. We discuss the possibility that such differences between Sbr+/Ssq- and Sbr-/Ssq+ conditioning may arise either from inherent differences in the responses of the animals to Sbr and Ssq, or, as seems more likely to us, from training and testing effects produced by differences in the compositions of the two stimuli.

Animals↗
PubMed1994

Pavlovian conditioning of morphine-induced alterations of immune status: evidence for peripheral beta-adrenergic receptor involvement.

The present studies examined the involvement of peripheral beta-adrenergic receptor activity in the establishment and expression of conditioned morphine-induced alterations of immune status. Previous work in our laboratory has shown that morphine's immunomodulatory effects can become conditioned to environmental stimuli which predict drug administration. These immune alterations include conditioned changes in natural killer cell activity, interleukin-2 production, and mitogen-induced lymphocyte proliferation. During the training phase of these experiments, Lewis rats received two conditioning sessions during which a subcutaneous injection of 15 mg/kg morphine sulfate was paired with exposure to a distinctive environment. On the test day, rats were reexposed to the conditioned stimulus prior to sacrifice. Saline or nadolol (0.002, 0.02, 0.2, or 2.0 mg/kg) was administered either prior to the training sessions or prior to the test session. Administration of nadolol prior to training did not affect the development of conditioned alterations of immune status. Conversely, nadolol administration prior to testing completely attenuated the expression of a subset of the conditioned morphine-induced changes in immune status. Taken together, these studies suggest that whereas peripheral beta-adrenergic receptor activity is not required for the establishment of conditioned morphine-induced alterations of immune status, it is involved in the expression of a subset of these conditioned immunomodulatory effects.

Animals↗
PubMed1998

Differential effects of NMDA-induced lesions into the insular cortex and amygdala on the acquisition and evocation of conditioned immunosuppression.

It has been established that the insular cortex (IC) mediates conditioned taste aversion, and recently we have demonstrated that lesions of this structure disrupt the acquisition of conditioned immunosuppression (CIS). The IC is functionally and reciprocally interconnected with the amygdala (AM) which has been suggested to be involved in neural-immune interactions. The aim of this work was to test the effects of NMDA-induced lesions in either the IC or AM in the acquisition (lesions made before conditioning) and evocation (lesions made after conditioning) of a conditioned immunosuppression task, obtained by one single pairing of saccharin taste and the immunosuppressive drug, cyclophosphamide. AM and IC lesioned rats were separated into four groups: the first two received lesions before and the other two were lesioned after the acquisition of conditioned immunosuppression. Twenty days after conditioning, animals were reexposed to saccharin and immunized with ovalbumin. After immunization, blood samples were taken, and analyzed by ELISA. The results showed that IC lesions disrupted the acquisition and evocation of CTA and CIS. Conversely, AM lesions disrupted only the acquisition of CIS. These data suggest that the IC is involved in the neural mechanisms underlying the acquisition and evocation of conditioned immunosuppression, and the amygdala could be important in mediating the input of the immune information necessary for the acquisition of conditioned immunosuppression.

Amygdala↗
PubMed1997

Type II glucocorticoid receptor antagonists impair contextual but not auditory-cue fear conditioning in juvenile rats.

There is evidence that glucocorticoids may play a role in learning and memory. To further explore this possibility, we examined the effect of the Type II glucocorticoid antagonists on contextual fear conditioning. This conditioning task is dependent on the hippocampal formation, a brain structure known to be rich in glucocorticoid receptors. Rats systemically injected with a Type II antagonist either 1 h prior to conditioning (RU 38486 and RU 40555) or immediately after conditioning displayed less contextual fear conditioning than rats injected with vehicle. Although RU impaired contextual fear conditioning, it had no effect on auditory fear conditioning. These data are consistent with other reports that contextual fear conditioning and auditory-cue fear conditioning depend on different processes and with the hypothesis that glucocorticoid activity contributes to the processes involved in the consolidation of some forms of memory.

Animals↗
PubMed2002

Posttraining prefrontal lesions impair jaw movement conditioning performance, but have no effect on accompanying heart rate changes.

This experiment examined the role of the medial prefrontal cortex (mPFC) in regulating learned autonomic and somatomotor responses in rabbits using appetitive Pavlovian conditioning. Interstimulus interval (ISI) duration [i.e., the time between the onset of the conditioned stimulus (CS) and unconditioned stimulus (US)] was manipulated in order to determine whether ISI duration was related to the heart rate (HR) responses obtained during conditioning. Two groups received either a 1- or a 4-s ISI, with a tone as the CS and an intraoral pulse of water as the US. Another two groups received explicitly unpaired presentations of either the 1- or 4-s tone CS and water US. Few conditioned jaw movement (JM) or HR conditioned responses (CRs) were observed in the unpaired conditions. Significant JM conditioning was, however, elicited by the paired conditions, especially to the 4-s ISI. Consistent CS-evoked HR accelerations were observed in both ISI conditions. After five sessions of training, the mPFC was lesioned in half the animals. A separate group of paired animals received sham lesions. After surgical recovery, all animals received 3 days of postoperative training. During the first postoperative training session, JM CRs significantly declined in both groups with mPFC lesions in comparison to the groups with sham lesions. The mPFC lesions, however, did not affect the CS-evoked cardiac accelerations, which again occurred during postoperative training.

Animals↗
PubMedDate not supplied

Conditioning of nicotine effects on motility and behaviour in rats.

Nicotine produces behavioural signs which are, in part, characteristic of dopaminergic activation. In the present study, it was investigated, to which degree these signs can be conditioned. The drug produced dose-dependent (0.15-0.60 mg/kg s.c.) increases in locomotor activity, hyperkinesia and stereotyped sniffing. The effects produced by 0.6 mg/kg nicotine were significantly inhibited by mecamylamine (1 mg/kg i.p.), but only in part by haloperidol (0.2 mg/kg i.p.). In a subsequent series, the administration of nicotine (0.6 mg/kg s.c.) was repeatedly associated with well-defined environmental (conditioned) stimuli: a wire cage associated with an auditory and an olfactory stimulus. Another group was pseudoconditioned, a third group remained drug-naive. When the animals were given saline in presence of the conditioned stimuli 24 h after the last conditioning session, locomotor activity, hyperkinesia and stereotyped sniffing were significantly higher in conditioned than in pseudoconditioned and drug-native rats. Similarly, when the rats were injected with nicotine (0.6 mg/kg s.c.) in presence of the conditioned stimuli 24 h after the last conditioning session, locomotor activity and stereotyped sniffing were most pronounced in the conditioned animals. These results demonstrated that behavioural effects of nicotine can be conditioned. Phenomena of this kind might contribute to the addictive behaviour to nicotine.

Animals↗
PubMed1988

Conditioned tolerance to haloperidol- and droperidol-induced catalepsy.

The possible mechanisms of conditioned tolerance to the cataleptogenic effects of haloperidol and droperidol were studied in order to discriminate between "classical" and "conditioned" tolerance. Rats were conditioned by repeated administration (19-27 times) of haloperidol (1.5 mg/kg i.p.) or droperidol (1.5 mg/kg i.p.), respectively, in the presence of a sum of defined environmental (auditory, olfactory and tactile) stimuli. The animals were compared with pseudoconditioned rats, which underwent the same number of drug injections and exposures to the environmental stimuli, but neither were associated. In part of the experiments, one further group of rats was repeatedly treated with only solvent in the presence of the environmental stimuli. Rats conditioned with haloperidol or droperidol showed tolerance to the cataleptogenic effect of a test dose of haloperidol (1.5 mg/kg i.p.) or droperidol (1.5 mg/kg i.p.), respectively, when they were tested in presence of the defined conditioning stimuli. The rats conditioned with droperidol showed significantly less catalepsy than the pseudoconditioned animals 30 min after droperidol administration, whereas in rats conditioned with haloperidol, the catalepsy was less pronounced no sooner than 120 min after haloperidol administration. This was a manifestation of conditioned tolerance. In rats pseudoconditioned with droperidol, the catalepsy was similar to that produced by the drug in drug-naive rats, suggesting no classical tolerance due to repeated administration of the neuroleptic drug. The dopamine turnover in striatum or nucleus accumbens after administration of 1.5 mg/kg of haloperidol i.p. was not altered in rats conditioned with haloperidol when compared with pseudoconditioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

A conditioned anti-parkinsonian drug effect in the hemi-parkinsonian rat.

In two separate experiments contralateral rotation was classically conditioned in hemi-Parkinsonian rats. In the first experiment, ten rats with unilateral 6-hydroxydopamine lesions of the substantia nigra, which produced ipsiversive circling, were given five daily injections of the dopamine receptor agonist apomorphine (0.5 mg/kg) to induce circling contralateral to the lesion hemisphere. One half of the rats (the conditioning group) were placed in a novel environment for 15 min during each apomorphine treatment. Subsequently, when placed into this environment 3, 10, 17, and 24 days after the final apomorphine injection, the conditioning group spontaneously rotated contralateral to the lesion hemisphere, whereas a similarly drug-treated non-conditioned group spontaneously rotated ipsilateral to the lesion hemisphere. On day 26, all rats were given a 2.0 mg/kg injection of d-amphetamine, which generated ipsilateral rotation in all rats in their home environment, but when placed in the conditioning environment, the conditioned group rotated contralateral whereas the non-conditioned group rotated ipsilateral. In the second experiment, eight rats with unilateral destruction of dopamine neurons were given differential conditioning in two novel environments. In every case, environments associated with 0.5 mg/kg apomorphine treatment induced contralateral rotation when the rats were tested without drug but ipsilateral rotation in environments not associated with apomorphine. These findings suggest a role for respondent or Pavlovian conditioning in the pharmacological management of Parkinsonism.

Animals↗
PubMed1991

Conditioning of apomorphine effects: simultaneous analysis of the alterations in cortical electroencephalogram and behaviour.

The possible conditioning of pharmacological effects of apomorphine on the electroencephalogram was studied using telemetric recordings in rats. Previous studies have shown that apomorphine-induced stereotyped behaviour can be conditioned: after repeated pairings of defined stimuli with the drug effect, the presentation of the external stimuli alone elicited stereotype sniffing, licking, and gnawing. Since apomorphine, an agonist at dopamine receptors, also produces a characteristic EEG pattern with an increase of power in the alpha-1 band, the possibility that this effect could also be conditioned was studied. In fact, conditioning with a dose of 0.5 mg/kg apomorphine (s.c.) led to a significant increase in the number of short-lasting episodes with enhancement of the power in the alpha-1 range in the presence of the conditioned stimuli, according to a comparison of the results obtained in the conditioned group and those of the controls ("pseudoconditioned"). Moreover, behavioural studies were performed simultaneously in order to find possible correlations between conditioned effects on EEG and conditioned alterations in behaviour. In general, a fair correlation between the increase of power in the alpha-1 band and stereotyped behaviour was found. This was also the case during extinction, when the conditioned stimuli were repeatedly uncoupled from apomorphine administration: both behavioural parameters and EEG alterations showed similar time-courses and had almost disappeared during the fourth extinction session.

Animals↗
PubMed1987

Comparison of the ability of (+)-amphetamine and caffeine to produce environment-specific conditioning.

Animals with a history of receiving psychomotor stimulants in a specific environment show enhanced activity when injected with saline and placed there. In the present study, a Pavlovian paradigm was used to compare the unconditioned and conditioned activity effects of (+)-amphetamine (0.1, 0.5, 1.0, and 5.0 mg/kg), caffeine (0.1, 1.0, 10.0, and 30.0 mg/kg), and a saline group (n's = 6-12). Rats experienced conditioning days with either drug or saline injected IP prior to a 60-min session in the activity monitor and the alternate saline or drug injected in the home cage following the session. On test days, all animals received saline in the activity monitors. Results revealed that amphetamine produced environment-specific conditioning in a dose-dependent manner; previous experience with 0.5, 1.0, and 5.0 but not 0.1 mg/kg in the activity monitor resulted in conditioned activity. A caffeine dose of 10.0 mg/kg produced stimulant effects on conditioning days and previous experience with the 1.0, 10.0, or 30.0 mg/kg dose in the activity monitor led to conditioned activity on test days. However, on test days the control groups as well as the 30.0 mg/kg experimental group showed significantly reduced activity as compared to the saline group. Thus, it appeared that caffeine produced hypoactivity 23 h after injection. Amphetamine produced conditioning in a dose-dependent manner, and the appearance of significant unconditioned activity during conditioning sessions was not necessary or sufficient to produce a conditioned effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Sensory and associative effects of morphine and naloxone in classical conditioning of the rabbit nictitating membrane response.

In Experiment I, classical conditioning of the rabbit's nictitating membrane response was accomplished by the pairing of tone and light conditioned stimuli with a shock unconditioned stimulus applied to the paraorbital region of the head. Morphine (5 mg/kg) significantly retarded the acquisition of conditioned responses to both conditioned stimuli. Moreover, morphine had no effect on nonassociative responding (baseline responding or responding to tone and light stimuli) or on the latency and amplitude of the unconditioned response elicited by shock during the explicitly unpaired presentations of tone, light and shock stimuli. The retardant effect of morphine on acquisition of conditioned responses was blocked by naloxone (1 mg/kg). In Experiment II, morphine (0.2-10 mg/kg) had no effect on the intensity threshold of the shock unconditioned stimulus for elicitation of unconditioned responses or on the latencies of the elicited responses. However, morphine (5 and 10 mg/kg) did produce a small but significant decrease in the amplitude of unconditioned responses elicited by the two highest shock intensities employed (3 and 4 mA). This latter effect of morphine was completely blocked by naloxone (1 mg/kg). In Experiment III, morphine (5 mg/kg) blocked the sensory processing of a tone conditioned stimulus, in previously trained animals, as measured by a significant (24 dB) elevation in the intensity threshold of the conditioned stimulus for elicitation of conditioned responses and an increase in the latency of the elicited response. Naloxone (1 mg/kg) completely blocked the effects of morphine on the sensory processing of the tone-conditioned stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination.

In rats, conditioned place preferences are produced by morphine and conditioned place aversions produced by naloxone. In the present studies, several issues concerning the demonstration and interpretation of place conditioning findings were examined in a two-compartment (black and white) tilt box: (1) the responses of naive rats to testing, (2) place conditioning in rats with strong unconditioned biases to one of the sides, and (3) modifications of the testing situation so that naive rats respond to the black and white sides with a minimum of initial bias. Experiments involving manipulation of the conditions of training and testing, use of pentobarbital, and use of a three-compartment test box helped to control for morphine's ability to produce state dependent learning as an explanation of its conditioned place preference. In addition, we examined previous place conditioning studies that failed to show aversive effects of naloxone. These negative findings were suggested to be due to the use or procedures insensitive to aversive stimuli and to the IP administration of naloxone. Finally, in the course of the experiments, novel data on general parameters of the place conditioning were provided. Dose-response curves for subcutaneous (SC) morphine (0.04-5.0 mg/kg) and naloxone (0.02-5.0 mg/kg) were established. Conditioned preferences were also shown to occur after at three pairings of SC drug, and they were retained for at least 1 month.

Animals↗
PubMedDate not supplied

Unit responses of the secondary somatosensory cortex during defensive conditioning in cats.

Unit responses in the secondary somatosensory cortex during the formation and extinction of a defensive conditioned reflex to acoustic stimulation were investigated in chronic experiments on cats. In 21 of 28 neurons tested during defensive conditioning the firing pattern changed in accordance with the character of responses to electric shock reinforcement. Two types of conditioned-reflex unit responses were distinguished: excitatory and inhibitory. Most neurons responding to the conditioned stimulus by activation did so during the first 50 msec, which was 80-100 msec before the conditioned motor response. Considerable variability of the unit responses was observed during conditioning. By the time of stabilization of the conditioned-reflex connections the unit response to the conditioned stimulus was stable in form. The pattern of extinction of the conditioned unit activity was expressed as a decrease in the discharge frequency in responses of excitatory type and disinhibition of activity in the case of inhibitory responses.

Animals↗