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Effects of the nicotinic receptor blocker mecamylamine on radial-arm maze performance in rats.

Lesions of cholinergic neurons have been found by many investigators to impair choice accuracy in the radial arm maze. Because muscarinic receptor blockers, such as scopolamine, have also repeatedly been found to impair choice accuracy in the radial-arm maze, it has generally been thought that the critical effect of cholinergic lesions is the deafferentation of muscarinic receptors. The possible involvement of nicotinic receptors in the cholinergic bases of cognitive performance in the radial-arm maze has not been as well investigated. The present study examined the effects of the blockade of nicotinic receptors on performance of female Sprague-Dawley rats in the radial-arm maze. Acute administration of the the nicotinic receptor blocker, mecamylamine (10 mg/kg) was found to significantly impair radial-arm maze choice accuracy. This dose also caused a significant increase in response latency in the maze. The effect on choice behavior but not locomotor speed seemed to be due to the central effects of mecamylamine, because administration of the peripheral nicotine receptor blocker, hexamethonium (20 mg/kg), did not impair choice accuracy, even though it did increase response latency to a similar degree as the 10-mg/kg dose of mecamylamine. Lower doses of mecamylamine (2.5 and 5 mg/kg) did not impair choice accuracy. These results indicate that central nicotinic as well as muscarinic cholinergic receptors are involved with cognitive functioning.

Animals↗

Habituation of oral responding in adult rats.

The effects of repeated oral stimulation on ingestive responding were investigated in adult rats. A series of brief intraoral infusions of flavored diet was delivered to female rats once every minute through an oral cannula. When the flavor of the infused diet remained constant, significant decreases in mouthing behavior were observed by the end of testing, whereas switching the flavor of the diet during testing resulted in enhanced responding and infusions delivered through gastric cannulas produced minimal effects. Patterns of oral responding were also similar in food-restricted rats. These patterns of responding suggest that adult rats habituate to oral stimulation. Finally, oral habituation led to decreased ingestion, whereas gastric infusions had minimal effects. Thus, oral habituation may represent a mechanism influencing intake in rats at all ages.

Animals↗

[Centenary of I.P. Pavlov's Madrid speech (April, 1903): Subjective aspect of mental activity as an object of system analysis].

The main pathstones of methodological approaches to objective exploration of mental activity outlined by I.P. Pavlov in 1903, in particular, such its features as the ability to forsee the results, expediency, reasonable character, and adaptivity of behavior are considered. Stages of methodological perfection of investigations of the inner (mental) states of living organisms, semantic transformation of conditioned reflex, conditioning of the first and second orders, systems of conditioned reflexes, psychonervous activity, causal and extrapolative reflexes are analyzed. The significance of the development of the theory of the functional system by P.K. Anokhin and the modern state of its understanding are shown. The functional significance and neurophysiologic mechanisms of movement task, programming, motivation, memory engram, reinforcement etc. is discussed.

Appetitive Behavior↗

Olfactory conditioning in the honey bee, Apis mellifera: effects of odor intensity.

Any odor-guided behavior might require generalization and/or discrimination over a wide range of odorant intensities. Proboscis extension conditioning (PEC) and electroantennogram (EAG) assays were used to investigate stimulus-intensity dynamics during olfactory processing in the honey bee. Experiments that tested generalization involved conditioning to one odorant concentration and either testing with a different odorant or with different concentrations of the same odorant. At low training concentrations, responses to either a novel odorant or to higher concentrations of the same odorant resulted in strong generalization. At higher training concentrations, significantly less generalization was observed to a novel odorant or to lower concentrations of the same odor. EAG analyses indicate that asymmetric generalization could arise due to long-term adaptation of peripheral receptor neurons. Discrimination experiments showed that relatively higher odorant concentrations associated with an appetitive reinforcer could usually be discriminated from a lower concentration that was associated with punishment, but not vice versa. Although sensory modulation in peripheral (sensory) processes might be sufficient to account for discrimination of a high from a low concentration, discrimination of low from high concentrations point to the involvement of central processes.

Animals↗

Instinctive predatory behavior of mustelids (Mustela putorius f. furo, Mustela vison f. dom.) modified by benzodiazepine derivatives.

The predatory behavior of the ferret and of the mink consists mainly of instinctive behavioral patterns that are elicited by simple external stimuli. An important stimulus is size of the prey; the time needed to catch and kill defensive prey depends on the size of the prey in relation to that of the predator. Benzodiazepine derivatives like chlordiazepoxide or lorazepam affect the prey catching of both species significantly. Drugged animals (2 mg/kg orally) need less time to overpower their prey. The experiments indicate that low concentrations of benzodiazepine derivatives disinhibit mustelids when hunting relatively large prey.

Animals↗

Choice as a function of local versus molar reinforcement contingencies.

Rats were trained on a discrete-trial probability learning task. In Experiment 1, the molar reinforcement probabilities for the two response alternatives were equal, and the local contingencies of reinforcement differentially reinforced a win-stay, lose-shift response pattern. The win-stay portion was learned substantially more easily and appeared from the outset of training, suggesting that its occurrence did not depend upon discrimination of the local contingencies but rather only upon simple strengthening effects of individual reinforcements. Control by both types of local contingencies decreased with increases in the intertrial interval, although some control remained with intertrial intervals as long as 30 s. In Experiment 2, the local contingencies always favored win-shift and lose-shift response patterns but were asymmetrical for the two responses, causing the molar reinforcement rates for the two responses to differ. Some learning of the alternation pattern occurred with short intertrial intervals, although win-stay behavior occurred for some subjects. The local reinforcement contingencies were discriminated poorly with longer intertrial intervals. In the absence of control by the local contingencies, choice proportion was determined by the molar contingencies, as indicated by high exponent values for the generalized matching law with long intertrial intervals, and lower values with short intertrial intervals. The results show that when molar contingencies of reinforcement and local contingencies are in opposition, both may have independent roles. Control by molar contingencies cannot generally be explained by local contingencies.

Animals↗

Increasing foraging opportunities for a group of captive capuchin monkeys (Cebus capucinus).

Capuchin monkeys often employ complex manipulative skills while recovering food items. Five captive Cebus capucinus were presented with two identical feeders that required the monkeys to lift up flaps, search through hay, and perform coordinated hand movements in order to obtain food items. The intent of this study was not to merely increase the amount of time the animals spent feeding, but to provide opportunities for greater expression of species-typical foraging behavior. In addition to their regular diet, figs and various types of unshelled nuts were placed inside the feeders. The monkeys avidly searched for and removed food from the feeders, displaying a wide variety of manipulative abilities. The amount of time the animals spent foraging significantly increased (p less than 0.05) whereas the amount of time the animals spent locomoting and resting significantly decreased (p less than 0.05) when the feeders were available. The feeders were portable, durable, easy to clean, and relatively inexpensive.

Animal Husbandry↗

The roles of cannabinoid and dopamine receptor systems in neural emotional learning circuits: implications for schizophrenia and addiction.

Cannabinoids represent one of the most widely used hallucinogenic drugs and induce profound alterations in sensory perception and emotional processing. Similarly, the dopamine (DA) neurotransmitter system is critical for the central processing of emotion and motivation. Functional disturbances in either of these neurotransmitter systems are well-established correlates of the psychopathological symptoms and behavioral manifestations observed in addiction and schizophrenia. Increasing evidence from the anatomical, pharmacological and behavioral neuroscience fields points to complex functional interactions between these receptor systems at the anatomical, pharmacological and neural systems levels. An important question relates to whether these systems act in an orchestrated manner to produce the emotional processing and sensory perception deficits underlying addiction and schizophrenia. This review describes evidence for functional neural interactions between cannabinoid and DA receptor systems and how disturbances in this neural circuitry may underlie the aberrant emotional learning and processing observed in disorders such as addiction and schizophrenia.

Amygdala↗

The effects of nicotine on learning and memory: a neuropsychological assessment in young and senescent Fischer 344 rats.

The effects of chronic nicotine on the behavioral performance of young (4 month) and old (24 month) Fischer-344 rats were assessed on four behavioral tasks: activity chamber. rotating rod, serial pattern learning, and Morris water maze paradigm. Old and young nicotine-treated rats received an intraperitoneal injection of nicotine (0.20 mg/kg) 15 min prior to all behavioral testing, and old and young saline-treated rats received saline injections 15 min prior to all behavioral testing. Nicotine improved motor coordination and increased the general activity levels of the old rats compared to old saline-treated rats. There were no significant differences in the behaviors of the young rats in these behavioral evaluations. In young rats, nicotine improved the acquisition of a serial pattern, suggesting an improvement in working memory or related processes. Nicotine was found to increase swim speed in a Morris water maze paradigm with a hidden platform; however, no beneficial effects of nicotine in reference memory were obtained for either age group. These results suggests that nicotine may not be as beneficial in attenuating age-related learning and memory deficits as once proposed.

Age Factors↗

Inhibition of p-chlorophenylalanine-induced muricide behavior following TRH microinjection into the limbic structures in the rat.

The effect of central microinjections of thyrotropin releasing hormone (TRH) on muricide behavior was investigated in rats with chronically implanted cannulas into one of the limbic structures: the amygdala, the hippocampus or the nucleus accumbens. The rats were made aggressive by p-chlorophenylalanine administration. Saline injection did not inhibit muricide, whereas TRH (10 micrograms in 0.5 microliter per side) significantly suppressed mouse-killing reaction upon injection into each of three regions. It is suggested that the observed antiaggressive effect of TRH may involve stimulation of the central noradrenergic and/or serotonergic transmission.

Amygdala↗

Firing rate of nucleus accumbens neurons is dopamine-dependent and reflects the timing of cocaine-seeking behavior in rats on a progressive ratio schedule of reinforcement.

The progressive ratio (PR) schedule of reinforcement is used to determine the reinforcing properties of rewards such as drugs of abuse. In this schedule, the animal is required to press a lever a progressively increasing number of times to receive a reward; the highest ratio obtained before the animal ceases responding is termed "breakpoint." We recorded neuronal spike activity from cells in the nucleus accumbens (NAc) of rats responding on a PR schedule for cocaine reinforcement. A common subtype of NAc cells demonstrated firing rates that varied according to the time between cocaine deliveries. The firing rate was inversely related to the NAc cocaine level predicted by a pharmacokinetic model. At higher response-to-reward ratios, inter-reward intervals were increased, resulting in a decrease in modeled cocaine level and a concomitant increase in firing rate over the session. The final increase in firing rate above a threshold value suggests a neural correlate of breakpoint. The effects of preadministration of dopamine D1 or D2 antagonists on the animals' behavior were similar in that both reduced breakpoint; however, each antagonist had markedly different effects on NAc cell firing. The D1 antagonist SCH23390 reduced firing rates, even at low cocaine levels, whereas the D2 antagonist eticlopride induced a rightward shift in the dose dependence of NAc cell firing relative to modeled cocaine level. Our results suggest that the firing of NAc cells reflects changes in cocaine levels and thereby contributes to the temporal spacing of self-administration and to the cessation of responding at breakpoint.

Animals↗

Lack of comprehension of cause-effect relations in tool-using capuchin monkeys (Cebus apella).

Four tufted capuchin monkeys (Cebus apella), successful in a tool task in which they used a stick to push a reward out of a tube, were tested in a similar task, with a tube with a hole and a small trap. Depending on where the stick was inserted, the reward was pushed either out of the tube or into the trap. With the trap-tube task, we assessed whether the monkeys understood the cause-effect relation between their behavior and the outcome. In Experiment 1, each subject underwent 14 10-trial blocks with the trap tube. Three subjects performed at chance level. The 4th subject's (Rb) performance improved, reaching 95% success in the last 6 blocks. In Experiment 2, Rb received additional tests to investigate its successful strategy further. Rb solved the trap-tube task by means of a distance-based, associative rule. The performances of the 4 subjects indicate that they did not take into account the effects of their actions on the reward.

Animals↗

Mutations that prevent associative learning in C. elegans.

The nematode Caenorhabditis elegans offers a promising system for the reductionist study of learning and memory. In this article, classical conditioning in C. elegans is demonstrated with a variety of associative learning assays. These assays allowed for the isolation and behavioral characterization of 2 mutant C. elegans lines impaired in associative learning. Both lines show no short-term or long-term associative conditioning; however, they appear relatively normal in tests of nonassociative learning and sensorimotor function. In combination with the well-described genetics and neuroanatomy of C. elegans, the isolation of mutants selectively, yet completely, blocked in associative learning provides the basis for an effective characterization of the cellular and molecular aspects of associative learning.

Animals↗

Dopaminergic mechanism of imipramine action in an animal model of depression.

Rats, subjected chronically (10-12 weeks) to a variety of mild, unpredictable stressors, showed a decrease in their consumption of weak sucrose solutions; normal behavior was restored by chronic (5-9 weeks) treatment with the tricyclic antidepressant imipramine. Acute administration of the dopamine receptor antagonist pimozide or the specific dopamine D2 receptor antagonist raclopride had no effect in nonstressed animals and in vehicle-treated stressed animals, but both drugs selectively reversed the improvement of performance in imipramine-treated stressed animals. The 5HT antagonist metergoline increased sucrose consumption in all groups. The data suggest that the mechanism of action of imipramine in this model is an increase in functional activity at dopamine (DA) synapses.

Animals↗

A nitric oxide agonist stimulates consolidation of long-term memory in the 1-day-old chick.

Chicks, age 1 to 2 days, that have been trained on a passive avoidance task with a strongly reinforced training trial yield a memory trace that is composed of 3 behaviorally and pharmacologically distinguishable stages, with the final long-term memory stage being dependent on protein synthesis. In contrast, chicks trained with a weakly reinforced learning trial typically do not demonstrate this final stage of memory. Sodium nitroprusside 150 microM intracranially administered immediately after a weak training trial promoted the formation of long-term memory, whereas saline did not. The results suggest that nitric oxide synthesis is either itself critical or stimulates other processes that are critical for the consolidation of long-term memory.

Age Factors↗

Cholinergic drug effects on a delayed conditional discrimination task in the rat.

The centrally acting cholinergic antagonist scopolamine (0.025-0.10 mg/kg ip) and the peripherally acting cholinergic antagonist methyl-scopolamine (0.01-0.10 mg/kg) dose dependently impaired discriminability independent of delay in a delayed conditional discrimination task that precludes use of mediating behavior. This indicates that scopolamine does not specifically affect working memory. Drugs that enhance cholinergic transmission neither improved discriminability nor attenuated scopolamine-induced impairments. In a post hoc analysis scopolamine was found to impair discriminability in a delay-dependent manner in rats that performed at a high level in pretest sessions. Methyl-scopolamine impaired performance independently of delay in these rats. The authors suggest that a ceiling effect at short delays produced this Drug x Delay interaction of scopolamine in the best performing rats.

Animals↗

Modulation of neuron activity in the basal forebrain of the rat related to the outcome of food-procuring movements.

Neuron activity was recorded from the basal forebrain of rats, including the mixed area of the ventral pallidum, substantia innominata, and mid part of Meynert's nucleus. The base of the forebrain was found to contain neurons (40% of all neurons recorded) which altered their activity on acquisition of a food-procuring skill in conditions of free behavior, depending on the outcome of the acquired movement reaction. The discharge frequencies of these cells increased when the animal obtained food from the feeder. When the rat was unable to procure the food, the discharge frequency of these cells either remained constant or decreased. Most of the neurons (57.1% of all neurons showing modifications) demonstrated modulation of their activity towards the end of the food-procuring movement, but before it was completed. A smaller proportion of the cells (35.7%) changed their activity after food was retrieved from the feeder.

Action Potentials↗

Enhanced food-related motivation after bilateral lesions of the subthalamic nucleus.

Although inactivation of the subthalamic nucleus (STN) has beneficial effects on motor symptoms of parkinsonism, little is known of possible actions on nonmotor symptoms of cognition or mood. Here, we used several forms of converging evidence to show that STN lesions can enhance behavioral motivation. Thus, bilateral fiber-sparing lesions of the STN in rats reduced the time required to eat a standard number of food reward pellets, without affecting food intake, and altered performance on a number of behavioral measures consistent with enhanced motivation for food. Thus, STN-lesioned rats showed greater levels of locomotor activity conditioned to food presentation, enhanced control over responding by food-related conditioned reinforcers, and a higher breaking point associated with elevated rate of lever press under a progressive ratio schedule of reinforcement. These results reveal a new functional role schedule for STN, possibly because of its involvement in ventral, as well as dorsal, striatal circuitry and are relevant to the therapeutic effects of STN stimulation in Parkinson's disease.

Analysis of Variance↗