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PubMed1992

Conditioning using a cerebral cortical conditioned stimulus is dependent on the cerebellum and brain stem circuitry.

Electrical stimulation of the auditory cortex (AC) was used as a conditioned stimulus (CS) in the rabbit conditioned eyeblink preparation to trace the functional anatomical connections between the AC and the circuitry underlying this conditioned response. Conditioning was shown to be dependent on the cerebellar interpositus nucleus and the pontine nuclei (PN), structures that are essential for conditioning using a peripheral CS. The results suggest that the cerebellum and associated brain stem circuitry are a necessary part of the memory trace circuit for the conditioned eyeblink response, even when the cerebral cortex is artifically engaged as a CS by electrical stimulation. The results also suggest that the PN are a site of convergence between the CS circuit subserving classical conditioning for peripheral stimuli and the AC, and may therefore be a site where the AC can modulate more elaborate forms of conditioning.

Animals↗
PubMed1998

Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat.

The hippocampus is believed to be an important structure for learning tasks that require temporal processing of information. The trace classical conditioning paradigm requires temporal processing because the conditioned stimulus (CS) and the unconditioned stimulus (US) are temporally separated by an empty trace interval. The present study sought to determine whether the hippocampus was necessary for rats to perform a classical trace fear conditioning task in which each of 10 trials consisted of an auditory tone CS (1 5-s duration) followed by an empty 30-s trace interval and then a fear-producing floor-shock US (0.5-s duration). Several weeks prior to training, animals were anesthetized and given aspiration lesions of the neocortex (NEO; n = 6), hippocampus and overlying neocortex (HIPP; n = 7), or no lesions at all (control; n = 6). Approximately 24 h after trace conditioning, NEO and control animals showed a significant decrease in movement to a CS-alone presentation that was indicative of a conditioned fear response. Animals in the HIPP group did not show conditioned fear responses to the CS alone, nor did a pseudoconditioning group (n = 7) that was trained with unpaired CSs and USs. Furthermore, all groups except the HIPP group showed conditioned fear responses to the original context in which they received shock USs. One week later, HIPP, NEO, and control animals received delay fear-conditioning trials with no trace interval separating the CS and US. Six of seven HIPP animals could perform the delay version, but none could perform the trace version. This result suggests that the trace fear task is a reliable and useful model for examining the neural mechanisms of hippocampally dependent learning.

Acoustic Stimulation↗
PubMedDate not supplied

Fear develops to the conditioned stimulus and to the context during classical eyeblink conditioning in rats.

In classical eyeblink conditioning, non-specific emotional responses to the aversive shock unconditioned stimulus (US), which are presumed to coincide with the development of fear, occur early in conditioning and precede the emergence of eyeblink responses. This two-process learning model was examined by concurrently measuring fear and eyeblink conditioning in the freely moving rat. Freezing served as an index of fear in animals and was measured during the inter-trial intervals in the training context and during a tone conditioned stimulus (CS) presented in a novel context. Animals that received CS-US pairings exhibited elevated levels of fear to the context and CS early in training that decreased over sessions, while eyeblink conditioned responses (CRs) developed gradually during acquisition and decreased during extinction. Random CS-US presentations produced a similar pattern of fear responses to the context and CS as paired presentations despite low eyeblink CR percentages, indicating that fear responding was decreased independent of high levels of learned eyeblink responding. The results of paired training were consistent with two-process models of conditioning that postulate that early emotional responding facilitates subsequent motor learning, but measures from random control animals demonstrate that partial CS-US contingencies produce decrements in fear despite low levels of eyeblink CRs. These findings suggest a relationship between CS-US contingency and fear levels during eyeblink conditioning, and may serve to clarify further the role that fear conditioning plays in this simple paradigm.

Animals↗
PubMed2002

Stimulation of serotonin1B receptors induces conditioned place aversion and facilitates cocaine place conditioning in rats.

RATIONALE: Changes in serotonin(1B) (5-HT(1B)) receptor function appear to modify the reinforcing properties of cocaine, but the direction of this effect is not completely clear. Pharmacological stimulation of 5-HT(1B) enhanced the rewarding properties of self-administered cocaine while attenuating the threshold-reducing effect of cocaine in the intracerebral brain stimulation procedure. OBJECTIVE: The present study investigates how pharmacological modification of 5-HT(1B) receptor-mediated neurotransmission influence cocaine motivational properties in the conditioned place preference paradigm in rats. METHODS: In separate groups of rats the motivational properties of CP 94,253, a selective 5-HT(1B) agonist, or GR 127935, a 5-HT(1B/D) receptor partial agonist, given alone or in combination, were determined. To evaluate their influence on cocaine-induced place conditioning, CP 94,253, that was found to be aversive, was given every day before each conditioning session, while GR 127935, which given alone had no effect, was administered only before cocaine conditioning sessions. RESULTS: CP 94,253, injected IP at 2.5 and 10 (but not 0.5) mg/kg produced place aversion in the place conditioning paradigm. The aversive effect of 2.5 mg/kg CP 94,253 was completely reversed by 10 mg/kg SC GR 127935. Given before every conditioning session, CP 94,253 did not modify place conditioning by four injections of 10 mg/kg cocaine but at 2.5 mg/kg it potentiated a sub-threshold dose of cocaine. The place preference caused by these two drugs was completely reversed by 10 mg/kg GR 127935. The antagonism by GR 127935 of CP 94,253's effects was shown not to be due to the induction of state-dependent effects. CONCLUSION: The results suggest that stimulation of 5-HT(1B) receptors causes place aversion, and enhances the effect of low doses of cocaine in the conditioned place preference paradigm.

Animals↗
PubMed1987

Involvement of cortical and thalamic auditory regions in retention of differential bradycardiac conditioning to acoustic conditioned stimuli in rabbits.

Our previous findings indicate that lesions in the medial division of the medial geniculate nucleus (mMGN) prevent the acquisition of differential conditioning of bradycardia to acoustic stimuli in rabbits. In the present experiment, the effect of lesions in mMGN on retention of differential bradycardiac conditioning was examined. In addition, the possible involvement of auditory cortex in differential conditioning was investigated. Electrodes were chronically implanted in mMGN, the ventral division of the medial geniculate nucleus (vMGN), or auditory cortex. After 7 days of recovery, animals received one differential Pavlovian conditioning session. At the end of the session, lesions were produced through the implanted electrodes. All animals demonstrated differential bradycardiac conditioning during the prelesion session. Animals with vMGN lesions also demonstrated differential conditioning during the postlesion session. However, mMGN and auditory cortex lesion animals failed to demonstrate differential conditioning during the postlesion session due to an increased response magnitude to the unpaired tone (CS-). These data support the hypothesis that mMGN plays a role in differential conditioning of bradycardia to tonal stimuli. In addition, these findings suggest that a possible corticothalamic pathway may be involved in the inhibition of the response to the CS-.

Acoustic Stimulation↗
PubMed1984

Conditioned stimulus intensity: role of cutaneous fiber size in classical conditioning of the flexion reflex in the spinal cat.

Three intensities of the conditioned stimulus (CS) were used to investigate the role of cutaneous fiber size on classical conditioning of the flexion reflex in the spinal cat. Conditioning occurred when the CS activated A alpha and A delta cutaneous fibers; CS activation of only the largest myelinated (A alpha) fibers or CS recruitment of unmyelinated (C) fibers in addition to A alpha and A delta fibers did not lead to significant conditioning. Comparison with two unpaired CS-US control treatment groups showed that the facilitation of reflex output during conditioning was specific to pairing of the CS and US and was not a consequence of sensitization or differential habituation rates between paired (conditioning) and unpaired (control) groups. These results were comparable to those from intact animal conditioning studies and thus lend further support to the spinal conditioning preparation as an appropriate simplified system for investigations of neural mechanisms of learning.

Animals↗
PubMed2006

Reinstatement of conditioned reinforcing properties of cocaine-conditioned stimuli.

The aim of the present experiment was to investigate the effects of cocaine primes and exposure to foot shock stress on reinstatement of operant responding maintained by a cocaine-conditioned stimulus in rats never trained to actively self-administer cocaine. Following a baseline session of responding for a light-buzzer compound stimulus, rats underwent classical conditioning whereby the compound stimulus was paired with passive intravenous infusions of cocaine (vehicle, 0.5 or 1.0 mg/kg/inf). On subsequent test sessions, operant responding for the compound stimulus was re-assessed in the absence of cocaine. Finally, rats received a cocaine prime (20 mg/kg, i.p.) and foot shock stress prior to two separate test sessions assessing lever pressing for the cocaine-conditioned stimulus. It was found that the animals conditioned with cocaine displayed sustained responding on the lever activating the cocaine-conditioned stimulus. In addition, priming injections of cocaine reinstated responding for the light-buzzer compound stimulus, and this effect was proportional to the dose of cocaine received during classical conditioning. Foot shock stress also reinstated responding, but its effect was smaller and observed only in animals conditioned with the highest dose of cocaine. These findings suggest that cocaine primes and stress can induce reinstatement by reactivating the motivational value of cocaine-conditioned cues.

Animals↗
PubMed2004

Conditioned food aversion elicited by the temperature of drinking water as a conditioned stimulus in rats.

It is known that taste can act as a conditioned stimulus (CS) for conditioned food aversion. In the present study, in order to examine whether or not the temperature of drinking water can be a CS, we conducted behavioral experiments in Wistar rats. The following results were obtained: (1) The rats subjected to aversive conditioning to 5 or 40 degrees C distilled water could learn to avoid these CSs, but they did not avoid any taste stimuli. (2) The rats subjected to aversive conditioning to 5 or 40 degrees C 0.1 M sucrose developed a generalized avoidance to sucrose at any temperature. (3) When rats familiarized to 25 degrees C 5 mM saccharin-Na (Sacc) were subjected to aversive conditioning to 5 or 40 degrees C Sacc, they avoided the respective CS, but they did not generalize it to any other stimuli even if having the same temperature as the CS. (4) The rats which had undergone transection of the taste nerves (chorda tympani and glossopharyngeal nerves) could acquire the conditioned response to the temperature of the CS. These results suggest that rats can be conditioned to temperature aversion and that the taste nerves are not needed in the formation of this conditioning.

Animals↗
PubMed2001

Conditioned fear stimuli reinstate cocaine-induced conditioned place preference.

These studies examined the ability of a conditioned stimulus previously paired with footshock to reinstate cocaine-induced conditioned place preference. Male rats were given either odor or tone in a paired (PRD group) or explicitly unpaired (random, RND group) manner with footshock. All rats were subsequently trained in a cocaine conditioned place preference (CPP) task. Cocaine CPP was demonstrated in all groups. After CPP extinction, presentation of the conditioned fear stimulus produced a greater degree of reinstatement in PRD rats compared to the RND group. This was true whether the conditioned stimulus was odor or tone, but when odor was used as the conditioned stimulus, the RND group also partially reinstated cocaine CPP. In rats trained with tone as the conditioned stimulus, presentation of the tone during the test for reinstatement produced robust reinstatement of cocaine CPP only in the PRD, but not RND, group. In contrast, a subsequent priming injection with cocaine reinstated cocaine CPP equally in both RND and PRD groups. These studies indicate for the first time that conditioned fear stimuli induce reinstatement of cocaine CPP, and suggest that stimuli associated with prior stress may produce relapse in humans.

Animals↗
PubMed1993

Operant conditioning after temporal lobe lesions in man: conditional and simple discrimination learning.

Temporal lobe lesions have been found to impair the acquisition of classical conditional discrimination learning in an eyelid conditioning paradigm, with sparing of simple eyelid conditioning. In the present study, subjects with left or right temporal resections were compared with normal controls on two operant conditioning tasks using a conditional and a simple discrimination paradigm analogous to the previously reported classical conditioning tasks. Subjects with right temporal lesions, and to a lesser extent those with left temporal lesions, were impaired relative to frontal lobe and control subjects in the acquisition of a conditional discrimination within an operant conditioning setting. A subsequent experiment showed that both left and right temporal lobe subjects were unimpaired on a simple operant discrimination task. These findings are compatible with theory relating hippocampal function to the learning of if-then rules.

Adult↗
PubMed2002

Effects of the social conditions of housing through testing on cocaine-induced contextual sensitisation and conditioned locomotion in C57BL/6J mice.

The potential differential effects of isolated and collective housing through the testing phase on sensitisation to cocaine-induced locomotion, the subsequent conditioned locomotion and the context-dependent expression of sensitisation were examined in C57Bl/6J male mice. Sensitisation was first generated in mice receiving seven once-daily subcutaneous injections of either saline or 10 mg/kg cocaine, before being placed in a testing chamber (singly) or in their home cage. On Day 8, mice were tested for conditioned locomotion (under saline). On Day 12, after three daily sessions of reinstatement of sensitisation, they were tested for contextual sensitisation (under cocaine). Whereas little or no effect of housing on the development of sensitisation was found, postsensitisation conditioned activity was significantly greater in isolation-kept mice (in comparison with the group-kept animals) and the likelihood of inducing a context-dependent expression of sensitisation was greater in grouped-housed mice. The results indicate that some of the aspects of contextual sensitisation can be influenced by the social conditions of lodging, not only when these conditions start several weeks before or during previous developmental periods of animals life (as previously published), but also when social isolation or social grouping are initiated after sexual maturity and applied through the period of treatments and testing. Moreover, the differential effect of social conditions of lodging on conditioned activity and contextual expression of sensitisation disagrees with the excitatory conditioning account of contextual sensitisation.

Animals↗
PubMed1989

Heart rate conditioning with pentobarbital as a conditioned stimulus and amphetamine as an unconditioned stimulus.

Pentobarbital was injected into rats 20 min after they were placed in an apparatus where heart rates were recorded. Amphetamine was injected after they were removed from the apparatus 29-30 min later. A Pavlovian conditioned response (CR) began after three or four such trials in the form of a failure of conditioned rats to show the same decline in heart rate obtained in controls after the pentobarbital injection. On later trials, the amphetamine was not injected until 50 min after the pentobarbital, and the CR was most obvious during the period 30-50 min after the pentobarbital injection, an effect characteristic of Pavlovian delay conditioning. The pharmacological effects of pentobarbital were necessary for conditioning because the CR was not obtained (a) when normal saline was substituted for the pentobarbital after successful conditioning or (b) when saline was used instead of pentobarbital throughout. Because of the speed and effectiveness of the conditioning, we believe the mechanism responsible for it has homeostatic regulation as its natural role. It was puzzling that environmental cues seemed to have a role in the conditioned stimulus complex, because conditioning was not apparent when the drug-drug pairings were administered in the home cage.

Animals↗
PubMed1994

Water deprivation enhances fear conditioning to contextual, but not discrete, conditional stimuli in rats.

Water-deprived and nondeprived rats were fear conditioned with a discrete tone conditional stimulus (CS) and an aversive footshock unconditional stimulus (US). Twenty-four and 48 hr following conditioning, conditional fear to the tone CS and the context cues of the conditioning chamber, respectively, were assessed by measuring freezing behavior. Water deprivation had no effect on baseline responding to either tone or contextual stimuli. Following either 1 or 3 tone-shock pairings, however, water deprivation selectively enhanced conditional freezing to the contextual cues of the training chamber; conditional freezing to the tone was unaffected by water deprivation. These results are consistent with the view that water deprivation affects fear conditioning via an influence on the hippocampus.

Animals↗
PubMed1980

Disruption of conditioned taste aversion in the rat by stimulation of amygdale: a conditioning effect, not amnesia.

Two experiments were conducted to determine whether the disruption of conditioned taste aversion by delivery of amygdaloid brain stimulation during conditioning could be attributed to the stimulus properties of the brain stimulation. In Experiment 1, animals receiving brain stimulation (a) while drinking saccharin, (b) during the onset of LiCl toxicosis, or (c) in the interval between taste exposure and toxicosis drank significantly more saccharin solution during a 48 hr retest than implanted or unoperated controls receiving similar taste-toxicosis pairings. In contrast, a group receiving brain stimulation during both conditioning and retention trials developed a strong conditioned aversion. Experiment 2 confirmed that amygdaloid stimulation can form a compound with the taste of the saccharin solution. A small but significant aversion was displayed by groups exposed to brain stimulation plus taste during conditioning and to either taste alone or brain stimulation alone during the retest. Again, the group presented with brain stimulation and taste prior to and following LiCl toxicosis displayed a strong conditioned aversion. These data suggest that disruption of conditioned taste aversion with amygdaloid stimulation represents a conditioning effect, not amnesia.

Amygdala↗
PubMed2006

The neural substrates of amphetamine conditioned place preference: implications for the formation of conditioned stimulus-reward associations.

Associations formed between conditioned stimuli and drug reward are major contributors in human drug addiction. To better understand the brain changes that accompany this process, we used immunohistochemistry for c-Fos (a neuronal activity marker), synaptophysin (a marker for synaptogenesis) and tyrosine kinase B receptor (a neurotrophic factor receptor that mediates synaptic plasticity) to investigate the neural substrates of amphetamine-induced conditioned place preference in rats. Conditioned place preference was induced by both 1.0 mg/kg and 0.3 mg/kg doses of amphetamine. Furthermore, amphetamine conditioning increased the density of c-Fos-immunoreactive cells and these cells were fully colocalized with the tyrosine kinase B receptor in the dentate gyrus, CA1 field and basolateral amygdala. Amphetamine conditioning increased the density of synaptophysin-immunoreactive varicosities in all brain regions studied, except the nucleus accumbens shell and dorsolateral striatum. The degree of conditioned place preference was highly correlated with c-Fos-immunoreactive cell density in the basolateral amygdala and with the density of synaptophysin-immunoreactive varicosities in all mesolimbic regions studied. The latter correlation was particularly impressive for the ventral pallidum and basolateral amygdala. The formation of conditioned stimulus-amphetamine reward associations is accompanied by tyrosine kinase B receptor expression in the basolateral amygdala and dentate gyrus, CA1 and CA3 fields of the hippocampus. These data therefore suggest that the formation of conditioned stimulus-reward associations requires, at least in part, activation of amygdalar-hippocampal circuits.

Amphetamine↗
PubMed1989

Induced specific immunological unresponsiveness & conditioned behavioral reflexes, in functional isomorphism-meditation and conditioned specific unresponsiveness.

Detailed functional isomorphism had been observed (Freed, 1984) between induced (conditioned) immunogenicity and classical conditioned defensive reflexes, possibly as evolutionary adaptation against danger at micro and macro levels respectively. Similarly, functional isomorphism is postulated between conditioned specific tolerogenicity of the immunotolerance system and behavioral reflexes. Isomorphism requires that sensory signals elaborated with intrinsic (unconditioned) behavioral tolerogens as carriers do not subsequently combine classically with unconditioned aversive stimuli and evoke conditioned defensive responses. Unconditioned behavioral tolerogenic carriers were identified with behavioral (physiological) activities of Oriental meditation. Confirmation of conditioned behavioral tolerogenicity appeared in the unresponsiveness of Yogi mediators to sensory stimuli as reflected in unchanged alpha rhythms of their encephalograms. Conditioned behavioral specific unresponsiveness maintains the "quiet" of meditation and mediates the experience of Zen mediators, namely, sharpened, clearer perceptions and unresponsiveness to aversive components of current conditioned signals ordinarily reactivating residues of affect. Conditioned behavioral specific unresponsiveness has survival value.

Brain↗
PubMed1990

The amygdala central nucleus and appetitive Pavlovian conditioning: lesions impair one class of conditioned behavior.

Rats with neurotoxic lesions of the amygdala central nucleus (CN) were trained using appetitive Pavlovian conditioning procedures. Conditioned responses (CRs) that are representative of 2 classes of behavior were monitored. One type of CR resembled the orienting responses that were elicited by the conditioned stimuli (CSs) prior to pairing with food reinforcement: the other type of CR resembled the behavior elicited by food reinforcement itself. Holland (1977, 1984) has referred to these as CS-generated and unconditioned stimulus (US)-generated CRs, respectively. During differential conditioning, some lesioned and unlesioned rats received reinforced presentations of a visual cue and nonreinforced presentations of an auditory cue, and the others in each lesion condition received reinforced auditory and nonreinforced visual cue presentations. Relative to the control group, the CN-lesioned rats were impaired in the acquisition of CS-generated CRs to both visual and auditory CSs. Orienting responses and habituation to the CSs were, however, comparable for the lesion and control groups. Moreover, rats with CN lesions readily acquired the US-generated CRs. Thus, a specific class of conditioned behavior was impaired by CN damage. Many studies using aversive Pavlovian procedures have suggested that CN lesions impair fear conditioning. The present results suggest another role for CN in the conditioning of orienting/attentional responses.

Amygdala↗
PubMed1988

Evidence that the neural pathways involved in backward conditioning are different from those involved in forward conditioning.

Effects of forward and backward conditioned-unconditioned stimulus (CS-US) intervals on classical conditioning of the flexion reflex were examined in a spinal cat preparation. A less intense conditioned stimulus (CS) was employed (activation of A-alpha cutaneous fibers) compared to that of a previous study (activation of both A-alpha and A-delta cutaneous fibers). Interstimulus intervals (ISIs) ranging from +3.0 to -3.0 sec were examined in 9 experimental groups, and results contrasted to those of an explicitly unpaired control group. The ISI of -0.25 sec produced optimal backward excitatory conditioning, paralleling the previous results. However, in contrast to the previous study, no conditioning was observed in any of the forward ISI groups. These observations support the hypothesis that backward and forward conditioning may be fundamentally different phenomena, induced by CS activation of different spinal reflex pathways: backward conditioning involves spinal reflex pathways activated by A-alpha cutaneous fibers of the CS, while forward conditioning involves spinal reflex pathways activated by A-delta cutaneous fibers of the CS.

Animals↗