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PubMed1996

Effects of cerebroventricle administration of acidic fibroblast growth factor on conditioned taste aversion learning in rats.

Wistar strain rats were given acidic fibroblast growth factor (aFGF) or denatured aFGF into their cerebroventricle before taste aversion conditioning for saccharin solution. Animals administered with aFGF showed significantly lower aversion threshold for saccharin at the 1st day and preference ratios for saccharin vs distilled water at the 4th, 6th, and 7th day after the conditioning than those administered with denatured aFGF. These results suggests that aFGF in the cerebrospinal fluid facilitates acquisition of the conditioned taste aversion learning.

Animals↗
PubMed1988

Selective D1 and D2 dopamine agonists produce opposing effects in place conditioning but not in conditioned taste aversion learning.

The neurotransmitter, dopamine (DA), has been implicated in place conditioning but the role of D1 and D2 receptors has not been investigated. In Experiment 1, the effects of SKF 38393 (0, 0.01, 0.1, 1.0, 10.0 mg/kg) and quinpirole (0, 0.01, 0.1, 1.0, 2.0, 4.0 mg/kg), preferential D1 and D2 receptor agonists, respectively, were evaluated and compared to (+)-amphetamine (0, 0.01, 0.1, 1.0, 2.0, 4.0 mg/kg). The experiment consisted of three phases. During the preexposure phase, rats explored two distinctive end compartments adjoined by a small tunnel. The time spent in each compartment was recorded. During the 8-day conditioning phase, rats were treated with drug and confined to one compartment for 30 min. On alternate days, rats received saline and were placed in the opposite compartment. Test days occurred over the remaining three days during which drug-free animals explored both compartments. Rats conditioned with (+)-amphetamine demonstrated a dose-dependent increase in time spent in the drug-paired environment from preexposure to test indicating the establishment of a conditioned place preference. Treatment with quinpirole also resulted in a conditioned place preference, however, only an intermediate dose was effective. In contrast, SKF 38393 produced a dose-dependent decrease in time spent on the drug-paired side suggesting the establishment of a place aversion. The idea that D1 receptors may be exclusively involved in mediating the aversive properties of psychomotor stimulants was tested in Experiment 2 employing a conditioned taste aversion paradigm. The results did not support this notion; it was found that both quinpirole and SKF 38393 produced a conditioned taste aversion.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Comparative effects of quisqualic and ibotenic acid-induced lesions of the substantia innominata and globus pallidus on the acquisition of a conditional visual discrimination: differential effects on cholinergic mechanisms.

Two experiments tested the hypothesis that the deficits in conditional discrimination learning produced by ibotenic acid-induced lesions of the ventral pallidum and substantia innominata are produced by loss of the magnocellular cholinergic cells in the nucleus basalis and adjacent regions. Experiment 1 replicated the previously reported deficit in conditional learning produced by ibotenate-induced lesions of the ventral pallidum/substantia innominata, but failed to demonstrate any restoration of learning by a subchronic regimen of the acetylcholinesterase inhibitor physostigmine sufficient to produce significant (30%), but equivalent, degrees of inhibition in the frontal cortex of ventral pallidum/substantia innominata-lesioned or sham-operated rats. Experiment 2 examined the effects of quisqualic acid-induced lesions of the ventral pallidum/substantia innominata. According to most of the measures of learning employed, the quisqualic acid-induced lesion of the ventral pallidum/substantia innominata failed to impair conditional learning, even though the quisqualate-induced lesion produced greater degrees of cholinergic neuron destruction than the ibotenate-induced lesion, as measured in terms of reductions in cortical choline acetyltransferase activity (44% vs 27%). Although consideration of individual data suggested that very high (60%) levels of choline acetyltransferase reduction in Experiment 2 might have detrimental effects of conditional learning, the overall failure of the quisqualate-induced lesions of the ventral pallidum/substantia innominata to impair learning is to be contrasted with the significant behavioural effects of ibotenate-induced lesions. Histological and immunocytochemical analysis showed that the quisqualate-induced lesion, unlike that produced by ibotenate, tended to produce less damage to the overlying dorsal globus pallidus and to parvocellular neurons of the ventral pallidum/substantia innominata, thus implicating these nonspecific effects of ibotenate-induced lesions in their behavioural effects. The present results question previous interpretations of the behavioural effects of ibotenate-induced lesions of the ventral pallidum/substantia innominata in terms of damage inflicted on the cortically-projecting cholinergic cells of the nucleus basalis, and suggest that quisqualic acid, although also nonspecific in its excitotoxic effects, is nevertheless more selective for producing damage to cholinergic neurons in the ventral pallidum/substantia innominata than ibotenic acid.

Animals↗
PubMed1994

Learning of the conditioned eye-blink response is impaired by an antisense insulin-like growth factor I oligonucleotide.

The cerebellum is thought to be critically involved in learning and retention of several types of classically conditioned motor responses. We investigated whether insulin-like growth factor I (IGF-I) may constitute an intercellular mediator of a motor learning task because previous findings indicated that IGF-I from the inferior olive modulates glutamate-induced gamma-aminobutyric acid release by Purkinje cells in the cerebellar cortex. Synaptic plasticity of the Purkinje cell is thought to be instrumental in motor learning. We found that injection of an IGF-I antisense oligonucleotide in the inferior olive elicited a complete inhibition of conditioned eye-blink learning in freely moving rats. This blockage was reversible and recovered when the levels of cerebellar IGF-I returned to normal values. Injection of a sense oligonucleotide did not interfere with the acquisition of the conditioned response. On the other hand, retention of the conditioned response was not impaired by subsequent injection of the IGF-I antisense oligonucleotide, indicating that olivocerebellar IGF-I is essential for the acquisition of the conditioned eye-blink response but is not essential for its retention.

Animals↗
PubMedDate not supplied

Nitric oxide synthase inhibition impairs spatial navigation learning and induces conditioned taste aversion.

The free radical gas nitric oxide (NO) is formed from the amino acid precursor L-arginine in brain regions which are associated with learning and the formation of memory. We have previously reported that administration of the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-Name) impairs delayed recall in non-human primates but that, at higher doses, impairment is associated with aversive gastrointestinal side effects. The purpose of the present study was to examine the effects of L-Name on learning in a rat spatial navigation task and to assess the ability of L-Name to induce a conditioned taste aversion (CTA) to a novel sucrose solution in a two-bottle choice paradigm. In the Morris water maze. L-Name (5, 20, and 50 mg/kg) markedly impaired cued spatial learning required to locate a hidden platform on three consecutive days of testing, but did not affect general activity levels. These data also demonstrated the ability of L-Name to induce a potent CTA, though only with the 20 and 50 mg/kg doses. Both the impairment of learning and CTA were blocked by administration of a mole equivalent dose of L-arginine, indicating that attenuated NO activity was associated with both behavioral effects. These data demonstrate that inhibition of NO activity by L-Name induces significant and selective impairment of cognitive performance at low pharmacologic doses (< 20 mg/kg). However, with higher doses of NOS inhibitors, impairment may be a secondary effect of drug-induced malaise, possibly related to peristaltic dysregulation of gastrointestinal musculature. Therefore, conclusions as to the mediation of learning and memory processes by CNS NO may be difficult to interpret without the use of selective, centrally-acting compounds.

Animals↗
PubMed1998

Effects of intra-amygdala R(+) 7-OH-DPAT on intra-accumbens d-amphetamine-associated learning. II. Instrumental conditioning.

Rats were trained to associate an initially neutral conditioned stimulus (CS) with a response-independent, intra-accumbens infusion of d-amphetamine (the unconditioned stimulus; US). Elsewhere, we have reported that as a result of this training, presentations of the CS alone elicited a conditioned response consisting of increased locomotor activity and that acquisition of this conditioned response was enhanced by post-session, intra-amygdala infusion of the dopamine D3 receptor preferring agonist, R(+) 7-OH-DPAT. Here, in this same group of animals, we have examined the conditioned rewarding properties of the drug-associated CS by determining its ability to support the acquisition of a novel instrumental response in the absence of drug reward. Thus, rats were presented with two novel levers. Presentation of the drug-associated CS was made contingent upon depression of one of the levers (CR lever), while responding upon the other lever (NCR lever) had no programmed consequences. Preferential responding upon the lever delivering the drug-associated CS was observed despite a 6-week interval between CS-US training and the conditioned reward test. Intra-accumbens administration of d-amphetamine (0-20 microg) increased the control over behaviour exerted by the CS, increasing CR. but not NCR lever responding. In contrast, rats that received three pairings of an intra-accumbens infusion of d-amphetamine in combination with intra-amygdala infusion of R(+) 7-OH-DPAT, 3 weeks prior to testing, displayed similar rates of response upon both levers and were insensitive to the potentiation of responding for conditioned reward following intra-accumbens d-amphetamine. However, intra-accumbens d-amphetamine stimulated locomotor activity in a similar, dose-related manner in both groups. In this way, rats that had received intra-accumbens infusion of d-amphetamine in combination with intra-amygdala infusion of R(+) 7-OH-DPAT appeared exactly like control group rats, for which the CS had been paired with intra-accumbens d-amphetamine on a negative basis only. A locomotor activity test indicated that one behavioural consequence of intra-amygdala administration of R(+) 7-OH-DPAT was the reduction of the unconditioned locomotor response resulting from intra-accumbens administration of d-amphetamine. Hence, the present data demonstrate that the conditioned rewarding properties of a drug-associated CS are specific to the CS-US association and are relatively insensitive to decay over time. However, the rewarding properties of a drug-associated CS were selectively abolished following activation of amygdala D3 receptors during presentation of the drug reward. Potential explanations for this effect are discussed, including the possibility that intra-amygdala R(+) 7-OH-DPAT reduced the incentive value of the US.

Amygdala↗
PubMed1975

Learning: rapid aversive conditioning in the gastropod mollusk Pleurobranchaea.

Untrained Pleurobranchaea feed voraciously when presented food and withdraw from electrical shocks. We trained experimental animals in ten trials spaced 1 hour apart to withdraw from food alone by electrically shocking them if they fed or were indifferent to food. The greatest increase in the number of learned withdrawal responses occurred within 12 hours after conditioning, and was accompanied by long-lasting increased in the threshold and latency of feeding responses. Control animals, which received food and shock alternately (unpaired) every half hour, showed considerably weaker changes than experimentals. These control responses quickly returned to initial levels after conditioning.

Animals↗
PubMed1983

GABA-ergic drugs: effects on conditioning, memory and learning.

In order to study the role of GABA in behaviour, various GABA-mimetic and GABA-blocking drugs were tested for their effects on a conditioned avoidance response (CAR). Sodium valproate slowed the acquisition of CAR and failed to affect the latency of a well-learned CAR, but interestingly, showed a marked anti-conflict effect similar to that of benzodiazepine-derivatives. The similarity of effects of drugs such as benzodiazepines and sodium valproate, which are postulated to potentiate GABA-ergic transmission, suggests that GABA plays a role in conditioning, memory and learning.

Aminooxyacetic Acid↗
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↗
PubMed1991

Effect of learned behavior upon conditioned place preference to cathinone.

The purpose of this study was to examine whether first training rats to discriminate the stimulus cues produced by an indirect dopamine agonist, cathinone, would influence a subsequent test of preference. The conditioned place preference (CPP) paradigm was used to evaluate the reinforcing effects of l-cathinone in four differently treated groups of rats. Half of the animals were trained to discriminate the interoceptive cues produced by 0.8 mg/kg cathinone in a two-lever, food-motivated operant task. The other animals were equally divided between two groups, one receiving saline and noncontingent reinforcements on the same schedule as those trained to discriminate cathinone; the other group, the "yoked-control" rats, received the same cathinone and saline regimen of administration as the discrimination-trained animals. Results of CPP testing indicate that cathinone produced a statistically significant conditioned place preference only in the group trained to discriminate cathinone and not in the saline or yoked control groups. Furthermore, when half of the cathinone discrimination-trained rats were pretreated with the dopamine release inhibitor CGS 10746B, the conditioned place preference to cathinone was attenuated. The results would indicate that pairing cathinone with a nonpreferred environment tended to make the rat spend more time in that environment and the amount of time spent in the cathinone-associated environment can be increased by prior discrimination training and decreased by diminished dopamine function in the brain.

Alkaloids↗
PubMed1989

Retinal transplant-mediated learning in a conditioned suppression task in rats.

Retinae were transplanted from embryonic rats to a location over the midbrain of unilaterally anucleated newborn rats. At maturity, the rats were trained to "lever-press" for a food reward. By using a Pavlovian conditioned suppression paradigm, it was found that light delivered to the transplant could be recognized by the host rat as a conditioned stimulus, resulting in a reduced rate of lever pressing.

Animals↗
PubMed2005

Impairment of water maze behaviour with ageing is counteracted by maze learning earlier in life but not by physical exercise, food restriction or housing conditions.

Spatial learning and memory decline with ageing in humans as well as rats. We examined the influence of different interventions on male Sprague Dawley rats with respect to learning ability and memory at the age of 5, 10 and 18 months. The intervention and control groups were: (RW) voluntary exercise in running wheels, (PW) sedentary, food restricted (by about 25%) to keep them at pair weight with RW, (S1) sedentary, fed ad libitum, (TM) forced training in a treadmill, and, (S4) sedentary, fed ad libitum. The animals in all groups were housed individually except those in group S4, which were housed four in each cage. The ability of learning and memory was determined in the Morris water maze. The results showed a significantly better learning ability when young in comparison with their ability when having grown older. At the age of 18 months, the performance was significantly better in the subgroups which had received training also at the age of 10 months compared to the subgroups receiving their first training. None of the various interventions had any significant effect on these functions. Repeated training seems to be the best intervention with respect to retaining learning ability and memory.

Aging↗