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Neuron-like differentiation of PC12 cells treated with media conditioned by either sciatic nerves, optic nerves, or Schwann cells.

In previous works we reported the finding of neurotrophic activity in a serum-free Dulbecco's modified Eagle's medium conditioned by rat sciatic nerves, previously maintained in culture for 11 days. This medium produces rapid neuron-like differentiation of cultured PC12 cells, as revealed by an increase in the size of the cell body and by the extension of short and/or long neurites by most of the cells. Neuregulin present in the conditioned medium was demonstrated to play a key role in the observed differentiation. In the present work, taking into consideration those latter results, the neurotrophic activity of conditioned media prepared with sciatic and optic nerves cultured during days 1-4 and 9-12 were studied. Evaluation of the trophic activities of those media revealed an opposite timing in the activities of sciatic and optic nerves conditioned media. The activity of the sciatic nerve was not observed in the 1-4-day period, increasing then up to the 9-12-day period. On the contrary, the optic nerve conditioned medium was active in the 1-4-day period, decreasing down to the 9-12-day period. These results led us to explore the contribution of the different cellular constituents of those nerves to their neurotrophic properties. As a first step in that direction we also investigated the neurotrophic activity of media conditioned during 12 days by cultured Schwann cells isolated from rat sciatic nerves. The Schwann cell conditioned media did produce a rapid differentiation of the PC12 cells similar to that caused by the sciatic nerve conditioned medium, though of a lower magnitude. Variations in the trophic activities of the conditioned media used in the present work is discussed taking into consideration the production of trophic and inhibitory factors by the peripheral and central glial cells. The role played by the optic nerve glia and myelin is being investigated at present.

Animals↗

Dopaminergic substrates of cocaine-induced place conditioning.

Recently, Spyraki et al. (Brain Research, 253 (1982) 195-203) reported that cocaine-induced place preference conditioning was unaffected by blockade of central dopamine (DA) or norepinephrine function. In addition, systemic injections of the local anesthetic procaine produced place preference conditioning. The present study was undertaken to further evaluate the possible role of DA in cocaine-induced place conditioning. In Expt. 1, a partial replication of Spyraki et al., systemic cocaine (5.0 mg/kg, i.p.) produced significant place conditioning that was not disrupted with the DA antagonist pimozide (1.0 mg/kg, i.p.). In Expt. 2, cocaine was microinjected unilaterally into the lateral ventricles to eliminate peripheral local anesthesia. Cocaine (50.0 micrograms, i.c.v.) produced place conditioning and pretreatment with pimozide (1.0 mg/kg, i.p.) disrupted the effect. In Expt. 3, place conditioning was not observed when cocaine presentations (50.0 micrograms, i.c.v.) were paired with both compartments. The substrates of cocaine-induced place conditioning were further investigated in Expt 4: Procaine (250 micrograms, i.c.v.) did not produce place conditioning whereas the DA agonist bromocriptine (50.0 micrograms, i.c.v.) did. Results suggest the involvement of central DA in cocaine-induced place conditioning.

Animals↗

Classical conditioning of tone-signaled bradycardia modifies 2-deoxyglucose uptake patterns in cortex, thalamus, habenula, caudate-putamen and hippocampal formation.

The 2-[14C]deoxyglucose (2-DG) autoradiographic method was used to map metabolic activity in all telencephalic and diencephalic structures of the rat brain during and after classical conditioning. A trial was made of a 4-5 KHz frequency modulated tone (CS) paired with midbrain reticular stimulation (US). The unconditioned response was a rapid bradycardia elicited by the US. Alert rats were injected with 2-DG, placed in a sound-proof chamber, and subjected during 90 min to a given treatment: (1) the CS before conditioning, (2) the US alone, (3) the paired CS-US (acquisition), (4) the CS after conditioning (extinction), (5) the US prior to the CS (sensitization), (6) the unpaired CS-US (pseudoconditioning), (7) the CS after pseudoconditioning and (8) no stimulation. The prefrontal cortex showed discrete regions with enhanced 2-DG uptake during conditioning and pseudoconditioning. A columnar organization was well-defined in the posterior parietal cortex of rats subjected to CS-US pairing. The medial thalamus was greatly activated in all groups subjected to reticular stimulation. The dorsomedial nucleus showed its largest activation during conditioning. The lateral habenula and a caudal portion of caudate-putamen showed an overall increase in 2-DG uptake during conditioning. The hippocampal formation showed a specific pattern of metabolic activation during conditioning and after conditioning. A laminar densitometric analysis showed that 2-DG uptake was concentrated in a central band along the sides of the hippocampal fissure which corresponded to the molecular layers. Only this neuropil band of greater metabolic activity showed the learning-related changes. In addition, the hippocampal formation was the only nonauditory structure in the forebrain which clearly responded to the acquired signal value of the tone CS after conditioning. These changes revealed by 2-DG provide a first demonstration of forebrain substrates with localized metabolic alterations related to learning and reticular sensitization.

Animals↗

Asymmetric uptake of 2-deoxy-D-[14C]glucose in the dorsal cochlear nucleus during Pavlovian conditioning in the rabbit.

Uptake of 2-deoxy-D-[14C]glucose was measured during Pavlovian conditioning of the rabbit's nictitating membrane response by both qualitative autoradiography and by quantitative measurement of radioactivity in samples of brain tissue. Conditioning was accomplished by pairing a tone stimulus delivered to both ears with an air-puff stimulus delivered to the right eye. Infusion of 2-deoxy-D-[14C]glucose during the first day of conditioning when there was no evidence of acquisition or during the 7th day of conditioning when animals demonstrated 68% conditioned responses resulted in a significantly greater uptake of radioactivity by the caudal portions of the left as compared with the right dorsal cochlear nucleus. Similar changes were not observed in other auditory and non-auditory nuclei. Rabbits that had acquired conditioned responses across 6 days of training and were exposed only to the tone-conditioned stimulus on the 7th day of testing exhibited 69% conditioned responses but no asymmetry in the uptake of 2-deoxy-D-[14C]glucose. Control animals receiving unpaired presentations of tone and air puff or no stimulation did not acquire conditioned responses and did not demonstrate asymmetric uptake of radioactivity in the dorsal cochlear nucleus. These results indicate that the asymmetric uptake of radioactivity by the dorsal cochlear nucleus did not result from the effects of stimulation per se or the prior occurrence of learning but was due to the explicit pairing of the tone stimulus with the asymmetric delivery of the air puff. It would appear that the caudal dorsal cochlear nucleus not only serves as a signal transducer for auditory stimuli but also receives inputs from other sensory systems thus allowing it to both recognize when an auditory stimulus is followed by a biologically significant event and to transmit such information to other brain regions that are, in turn, responsible for learning.

Animals↗

Presynaptic dopaminergic neurotransmission mediates amphetamine-induced unconditioned but not amphetamine-conditioned locomotion and defecation in the rat.

A series of experiments were conducted to investigate the role of presynaptic dopamine (DA) and noradrenaline (NA) neurotransmission in stimulant-unconditioned and conditioned locomotion and defecation. (+)-Amphetamine (AMP, 1.5 mg/kg, s.c.) increased both locomotion and defecation in rats, and both of these effects were conditioned to environmental stimuli. Some groups of rats were treated with DSP4 (50 mg/kg, i.p.), a selective, long-lasting NA neurotoxin, given 7 days prior to conditioning with AMP. This treatment depleted forebrain NA to between 1% and 54% of control levels, depending on the brain region, but did not attenuate either AMP-unconditioned or conditioned locomotion. These results indicate that NA does not mediate either AMP unconditioned or conditioned locomotion. alpha-Methyl-para-tyrosine methyl ester (alpha MPT, 25-50 mg/kg, s.c.), a selective inhibitor of catecholamine synthesis given during conditioning with AMP, attenuated unconditioned AMP-induced locomotion and defecation but did not influence AMP-conditioned locomotion and defecation. Thus, alpha MPT blocked AMP-induced unconditioned locomotion, supporting the hypothesis that the locomotor and defecation stimulant effects of AMP are mediated by DA release. In spite of the attenuation of the direct effects of AMP, alpha MPT did not attenuate AMP-conditioned locomotion or defecation. It is concluded that AMP-induced release of dopamine is responsible for the unconditioned behavioral effects of amphetamine but not for the conditioning of amphetamine-induced locomotion and defecation.

3,4-Dihydroxyphenylacetic Acid↗

Ibotenic acid lesions in the amygdaloid central nucleus but not in the lateral subthalamic area prevent the acquisition of differential Pavlovian conditioning of bradycardia in rabbits.

The present study examined the effect of ibotenic acid lesions in the amygdaloid central nucleus (ACe) or in the lateral zona incerta of the subthalamus (LZI) on the acquisition of differential Pavlovian conditioning of bradycardia in rabbits. Previous work has shown that bilateral electrolytic lesions in either ACe or LZI abolished the retention of conditioned heart rate (HR) responses. In order to determine whether these findings were due to destruction of cells intrinsic to ACe or LZI, ibotenic acid lesions were placed bilaterally in either structure or in control sites. Following recovery, animals were subjected to differential Pavlovian conditioning in which one tone (CS+) was paired with periorbital shock and a second tone (CS-) was presented alone. It was found that destruction of cell bodies in ACe, but not LZI, prevented the acquisition of the differential bradycardiac conditioned response. In addition, ACe lesions did not interfere with baseline HR, the HR orienting response, the HR unconditioned response to shock, or the concomitantly conditioned corneoretinal potential. The results of this study suggest that destruction of cells intrinsic to ACe selectively prevents the acquisition of differentially conditioned HR, and perhaps other conditioned responses related to conditioned arousal, but does not affect unlearned HR responses or specific somatomotor conditioned responses.

Amygdala↗

Enhanced nociceptive behaviour following conditioning injection of formalin in the perioral area of the rat.

The possible existence of long-term modifications in response to a transient nociceptive conditioning stimulation was investigated in the rat in three experiments. (1) A nociceptive conditioning stimulus was delivered in the form of a s.c. formalin injection (conditioning injection) in the left upper lip. Evaluation of the nociceptive behaviour triggered by another formalin injection (testing injection) made in the controlateral right upper lip was carried out in distinct groups of rats 7, 14 or 28 days after the conditioning. An enhanced nociceptive response at day 7 and 14 and a return to the baseline at day 28 were observed. (2) A similar protocol was developed with formalin used for both conditioning and testing but an anaesthetic blockade of the infraorbital nerve was performed just before the conditioning injection to suppress the initial barrage. The change observed at day 7 was suppressed by the nerve block. (3) A conditioning nociceptive stimulus was applied either ipsilaterally to the right lower lip or to the tail. An increased nociceptive response was observed when the conditioning stimulus was applied to the same side as the test stimulus but no increase in the formalin test response was detected when the conditioning stimulus was applied to the tail. These results indicated that, after a single formalin injection in the left upper lip, a hyperexcitability developed that depended on the initial barrage, lasted for at least 2 weeks, was no longer present at 4 weeks and might rely on a segmental mechanism. The hypothesis of a central sensitization triggered by an initial barrage and maintained by an ongoing input induced from the periphery is discussed.

Animals↗

Evidence of Pavlovian conditioned fear following electrical stimulation of the periaqueductal grey in the rat.

Stimulation of the periaqueductal grey (PAG) has been used to support aversive conditioning in a variety of species with several experimental paradigms. However, it has not been clearly demonstrated whether the behavioral changes produced by PAG stimulation in these paradigms are mediated by associative or nonassociative mechanisms. The present studies demonstrate that electrical stimulation of the PAG in the rat may be used to support associative learning in a Pavlovian paradigm. In each experiment, a fully controlled conditional emotional response (CER) procedure was used to examine the unconditional aversive properties of PAG stimulation. In Experiment 1a, weak associative conditioning was observed when a light CS was paired with PAG stimulation over 6 conditioning trials. In Experiment 1b, robust associative conditioning was obtained with a light CS when 18 conditioning trials were used. In Experiment 2, robust associative conditioning was demonstrated with a tone CS when 6 conditioning trials were used. The results parallel those found when other aversive stimuli are used as a UCS (e.g., footshock or intraorbital air puff), and because the present experiments included the proper control procedures the results clearly indicate that the behavioral changes produced by PAG stimulation are mediated by associative Pavlovian learning mechanisms rather than nonassociative mechanisms such as sensitization or pseudoconditioning. The present technique may be useful for assessing the neuroanatomical and neurochemical substrates underlying the aversive effects of brain-stimulation, and for screening the effects of drugs on the conditional and unconditional responses produced by such stimulation.

Acoustic Stimulation↗

Role of auditory cortex in the acquisition of differential heart rate conditioning.

Previous findings from our laboratory indicate that lesions of the auditory cortex disrupt the retention of differentially conditioned bradycardiac responses to tonal stimuli in rabbits. In the present experiment, the effect of lesions of the auditory cortex on the acquisition of differential bradycardiac conditioning was examined. The effect of lesions in the auditory cortex were compared to the effect produced by control lesions in the visual cortex. After 7 days of recovery, animals received 7 days of differential Pavlovian bradycardiac conditioning in which one tone (CS+) was paired with the unconditioned stimulus, and another tone (CS-) was never paired with the unconditioned stimulus. All animals demonstrated differential conditioning during the first 3 days of conditioning. On days 4-7, however, auditory cortex lesioned animals did not exhibit significant differential heart rate (HR) conditioning, whereas control animals with lesions in the visual cortex showed no loss of conditioning during this period. The loss of differential conditioning in animals with lesions in the auditory cortex appears to be due to an increase in the magnitude of the response to the CS-. These data support the hypothesis that the auditory cortex serves to inhibit the response to the CS- in differential conditioning of bradycardia to acoustic stimuli, and that the inhibition may be mediated by a descending corticothalamic or corticolimbic pathway.

Animals↗

Modulation of body temperature through taste aversion conditioning.

Injection of rats with bacterial lipopolysaccharide (LPS) results in an initial fall in body temperature followed by a fever. Lithium chloride (LiCl) injection induces a fall in body temperature without subsequent fever production. When these substances were incorporated as unconditioned stimuli in a taste aversion conditioning paradigm, using saccharin flavour as the conditioning stimulus, these differential effects on body temperature were reenlisted on reexposure to saccharin alone 7 days after conditioning. The changes in body temperature on reexposure were similar in direction and kinetics as on the conditioning day although reduced in magnitude. The finding of a true conditioned effect in these studies is in contrast to the paradoxical or compensatory conditioned body temperature responses described elsewhere using different conditioning models. This apparent conflict may be explained on the basis of different unconditioned stimuli acting on efferent versus afferent arms of a negative feedback system. Since body temperature changes often occur in association with immune responses, these findings may have implications to behavioural conditioning of immunity, the outcome of which may reflect the indirect effects on immunity of inadvertent conditioning of thermoregulatory changes.

Animals↗

The postingestive consequences of fat condition preferences for flavors associated with high dietary fat.

To investigate whether children acquire conditioned preferences for flavors associated with high dietary fat content, 27 3- and 4-year-old children participated in a series of 12 conditioning or mere exposure sessions. Following an overnight fast, children who participated in conditioning trials consumed fixed quantities of a flavored yogurt drink that on half the days was high in fat and energy (954 kJ, 18 g fat/150 g serving) or contained no fat (277 kJ, 0 g fat/150 g serving). Children in the conditioning group consumed 150 g servings, children in the mere exposure group tasted 16 g or less of these same stimuli. Preferences were assessed before and after conditioning when the children were hungry and also postconditioning when the children were satiated. Results provided evidence for conditioned preferences based on the postingestive consequences of dietary fat. Children in the conditioning group learned to prefer the high-density paired flavor over the low-density paired flavor, and increased their preference for the high-density paired flavor from pre- to postconditioning. Children in the mere exposure group showed positive shifts in preference for both the fat-free and the high-fat paired flavors. In the conditioning group, preferences for the high-fat flavor was depressed by satiety, whereas the preference of the mere exposure group did not vary with hunger state. Conditioned flavor preferences, based on the postingestive consequences of fat intake, may contribute to children's preferences for foods high in dietary fat.

Association Learning↗

Further studies on nicotine-induced conditioned place preference in the rat.

Rats received subcutaneous (SC) injections of either nicotine (NIC, 0.001 to 2.0 mg/kg) or saline (SAL, 1 ml/kg) immediately prior to conditioning sessions in a conditioned place preference (CPP) paradigm. NIC was paired for 3 conditioning sessions with one environment of a 3 compartment CPP apparatus; SAL was paired with another environment. The animals were then tested for place preference by determining the proportion of time spent in each compartment during a 15 min test session. A dose-response curve was obtained for the place conditioning effect of nicotine as measured by its ability to alter baseline preferences calculated from control rats. NIC's place preference, but not place aversion, effect was linearly correlated with respect to dosage within the range of 0.1 to 0.8 mg/kg. NIC, 0.8 mg/kg, induced a place preference when it was administered immediately prior to conditioning sessions, but not when administered 20, 60 or 120 min prior to the sessions. Three repeated conditioning and testing cycles, or the daily administration of NIC for 2 weeks between conditioning and testing cycles had little or no effect on NIC place conditioning. Lobeline (2, 10 and 20 mg/kg) or cotinine (1 to 50 mg/kg) failed to condition a place preference. NIC, 0.1 or 1.2 mg/kg SC, administered to rat pups on postnatal days 5 through 8, did not alter subsequent place preference (induced by 0.8 mg/kg of NIC) measured at approximately 40 and 70 days of age. Periodic measurements of spontaneous motor activity, forelimb grip strength and negative geotaxis were unaltered by the perinatal exposure to nicotine.

Animals↗

Effects of LSD-25 on classical trace conditioning.

This study examined the effects of LSD-25 on the excitatory properties of auditory conditioned stimuli as a function of the interstimulus interval. The rabbit's eyeblink response was conditioned using a discriminative trace procedure by the pairing of a 500-msec auditory conditioned stimulus with a 100-msec shock unconditioned stimulus at intervals of 1000, 2000, 4000 and 8000 msec. Animals were able to acquire conditioned responses across all intervals. They then received doses of 35 or 85 micrograms/kg of LSD-25 prior to additional conditioning sessions. LSD-25 produced an increase in the magnitude of conditioned responses to both the positive and negative conditioned stimuli at all interstimulus intervals. It was concluded that LSD did not alter discriminative conditioning but rather enhanced the excitatory properties of both positive and negative conditioned stimuli.

Animals↗

Eyeblink conditioning deficits in the old cat.

Acquisition of a conditioned eyeblink reflex was studied in aged cats 10-23 years old and young cats one to three years old. All ten young cats became conditioned within 1,000 trials, after a mean of 270 trials, with a stimulus protocol including a 1500 msec 4 kHz tone CS+ followed by a shock unconditioned stimulus, and click CS-. Nine of 15 aged cats failed to become conditioned with 1,000 trials. Six old cats became conditioned after a mean of 522 trials. Four aged cats tested with a simpler protocol involving a 400 msec CS+ and no click CS- became conditioned with less than 500 trials. All retained the conditioned response when clicks were added to the 400 msec CS+. Three aged animals which failed to become conditioned with the 1500 msec CS+ and clicks were trained with an 800 msec CS+ without clicks. Only one became conditioned within 500 trials. Thus duration of the tone CS+ was critically important for acquisition of a conditioned eyeblink response by aged cats.

Aging↗

Awareness of the CS-UCS contingency and classical conditioning of skin conductance responses with olfactory CSs.

The possibility of demonstrating acquisition of classically conditioned responses without awareness of the conditioned stimulus-unconditioned stimulus (CS-UCS) contingency using olfactory stimuli with 58 college student subjects was tested. A classical discrimination delay conditioning paradigm was employed, with electric shock as the UCS and two pleasant odors (perfumes) as the conditioned stimuli (CS+ and CS-). Trial-by-trial measures of skin conductance conditioned responses served as dependent variables. A masking task in the form of an olfactory memory task was employed for the purpose of delaying the onset of awareness of the conditioning contingency. Awareness of the conditioning contingency was assessed by a concurrent and a post hoc measure, and subjects who satisfied both criteria were considered aware of the CS-UCS contingency. Conditioning was observed only in the aware subjects, and only after the onset of awareness of the CS+-UCS contingency. Respiratory activity, measured as a check against possible artifacts, had no effect on the SCR measures. It was concluded that the awareness of the CS-UCS contingency is necessary for acquisition of discriminative conditioned responses in humans, regardless of the sensory modality in which CSs are presented. Sex differences in skin conductance measures and performance on the olfactory memory task were observed.

Adult↗

Naltrexone blocks the expression of the conditioned elevation of natural killer cell activity in BALB/c mice.

An elevation of natural killer (NK) cell activity was conditioned by the association of a camphor odor conditioning stimulus (CS) with an injection of 20 micrograms polyinosinic:poly-cytidylic acid (poly I:C), the unconditioned stimulus (US). Poly I:C elicits the production and secretion of interferon (IFN), which induces an increase in NK cell activity. Reexposure to the CS occurred on Days 3 and 5 after the association trial on Day 0. Immediately following the CS exposure on Day 5, 1 microgram poly I:C was administered to all animals. This procedure resulted in an increased NK cell activity in the conditioned (CND), but not the nonconditioned (NC), mice. In this study we have shown that the expression of the conditioned response was blocked by an injection of naltrexone (NTX) at 10 mg/kg ip when given immediately prior to the two test CS odor exposures. Peripheral treatment (ip) with a quaternary form of naltrexone (QNTX), which is a less potent opiate antagonist, at the same dose and at the same time relative to the CS odor reexposure did not block the conditioned response. The formation of the conditioned association did not appear to be disrupted by NTX at the 10 mg/kg dose when given immediately prior to the trial odor exposure on Day 0. No modulation of NK cell activity was observed in any of the control groups treated with naltrexone or the quaternary analog. Because of the inability of the QNTX to block the conditioned response, we hypothesize that the opiate receptors involved in the conditioned response and blocked by NTX were within the central nervous system (CNS). Whether this response is peripherally or centrally mediated, we have shown that opiate receptors represent part of the mechanism which mediates the conditioned augmentation of NK cell activity.

Animals↗

Conditioned immunosuppression of a murine delayed type hypersensitivity response: dissociation from corticosterone elevation.

The mechanisms involved in behavioral modulation of immunity by Pavlovian conditioning have not been delineated, although an elevation in adrenocortical steroids has been invoked as an explanation. Therefore, we investigated whether or not a 4-day, murine delayed type hypersensitivity (DTH) response could be modified by a taste aversion conditioning paradigm. Mice were conditioned by the pairing of their saccharin (0.1%) drinking water (SAC) with a cyclophosphamide (CY) injection (50 mg/kg) on Day 0. Conditioned mice that were exposed on Day 3 to SAC + CY, SAC + normal saline, or water + CY exhibited significant suppression of DTH induced paw swelling when compared to nonconditioned controls. Conditioned immunosuppression was demonstrated, since the DTH response was suppressed by SAC without a concomitant reexposure to the immunosuppressant, CY. However, when dexamethasone (3 mg/kg) was used as the conditioning agent, the SAC + vehicle group showed no reduction in paw swelling. A serum corticosterone time course study was performed to examine possible involvement of glucocorticoids in conditioned immunosuppression. On Day 3, mice were sacrificed 30, 60, 90, 120 min and 24 h after reexposure to SAC or water. No significant differences in serum corticosterone levels were detected between nonconditioned controls and any conditioned group at any time point. These results demonstrate conditioned immunosuppression of a cell-mediated immune response that is not linked to a rise in glucocorticoid levels.

Animals↗

Haloperidol can increase responding to both discrete and contextual cues in trace conditioned rats.

Haloperidol has been shown to enhance attentional selectivity in conditioning procedures. For example, in latent inhibition (LI) it improves animals' ability to treat as irrelevant, stimuli that have previously been presented without consequence. The present study tested whether this finding would generalize to other procedures that present animals with weak predictors. We therefore used a trace conditioning procedure to present rats with a conditioned stimulus (CS) weakened through temporal discontiguity (rather than preexposure in LI) and a flashing light background provided an alternative experimental stimulus. In Experiment 1, a noise CS was paired contiguously (at '0 s') with food or at a 10 s trace interval. In Experiment 2, the trace interval was lengthened to 20 s. In both experiments, haloperidol treatment generally reduced responding in 0 s contiguous groups. By contrast, 0.03 mg/kg haloperidol enhanced conditioning, selectively, to the weakly predictive trace CS, though it was without effect on responding within the trace interval. In addition, again at 0.03 mg/kg, haloperidol significantly increased excitatory conditioning to contextual stimuli in trace groups relative to contiguous groups. At the shorter (10 s) Experiment 1 trace, this result was shown in the extinction test of conditioning to the background stimulus. At the longer (20 s) Experiment 2 trace, this result was shown in the acquisition of responding to the box context in the inter-trial-interval. The demonstration that low dose haloperidol can increase conditioning is novel. This increase was seen selectively with stimuli (both trace-conditioned and contextual) that should have been treated as weak predictors so these results are contrary to what was expected on the basis of haloperidol effects on stimuli weakened through pre-exposure. The possibility that increased contextual conditioning could be relevant to the interpretation of haloperidol-induced enhancement of LI is discounted. However, it is suggested that this result could nonetheless reflect cognitive enhancement.

Acoustic Stimulation↗