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PubMed1998

Discriminative stimulus properties of the 5-HT1A receptor agonist BAY x 3702 in the rat.

The aminomethylchroman derivative BAY x 3702 (R-(-)-2-¿4-[(chroman-2-ylmethyl)-amino]-butyl¿-1,1-dioxo-benzo[d] isothiazolone HCl) has recently been characterized as a relatively selective, high affinity 5-HT1A receptor agonist with neuroprotective, anxiolytic- and antidepressant-like effects in animal models. It was the aim of the present study to further confirm its receptor binding profile in an in vivo assay. Rats were trained to discriminate BAY x 3702 (0.1 mg/kg, i.p.) from vehicle in a standard two-lever fixed ratio 10 food-reinforced procedure. All rats learned the discrimination, the median number of sessions to reach criterion being 38 (range: 22-58 sessions). Generalization tests with BAY x 3702 showed dose-dependent and complete generalization after different routes of administration; the ED50 values being: 0.030, 0.007 and 0.36 mg/kg, after i.p., i.v. and p.o. administration, respectively. Assessment of the duration of action after administration of 0.1 mg/kg BAY x 3702, i.p., resulted in a T1/2 of 65 min. Dose-dependent and complete generalization was also obtained with the 5-HT1A receptor agonists 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin, ED50 in mg/kg, i.p.: 0.086), flesinoxan (0.30), SR 57746A ((4-(3-trifluoromethylphenyl)-N-(2-(naphth-2-yl)ethyl)-1,2,3,6-tet rahydropyridine HCl, 1.0), the (+)-enantiomer of BAY x 3702 (1.3) and ipsapirone (1.8); the ED50 values being closely correlated with their respective affinities for the 5-HT1A receptor. Pretreatment with the selective 5-HT1A receptor antagonist WAY-100635 ((N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N(2-pyridinyl) cyclohexane carboxamide trihydrochloride) dose-dependently and completely blocked the discriminative effects of 0.1 mg/kg BAY x 3702 (ID50: 0.013 mg/kg, i.p.). WAY-100635, prazosin, idazoxan, raclopride, paroxetine, (-)-BAY k 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-p yridine-5-carboxylate), ethanol, and the putative neuroprotectants MK-801 ((+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e), CNS 1102 (N-(1-naphthyl)-N'-(3-ethylphenyl)-N'-methyl-guanidine), CGS 19755 (cis-4-(phosphonomethyl) piperidine-2-carboxylic acid) and nimodipine did not induce more than 20% generalization. It is concluded that the BAY x 3702 cue is mediated by its agonistic activity at 5-HT1A receptors.

Administration, Oral↗
PubMed2002

Niche-related learning in laboratory paradigms: the case of maze behavior in Norway rats.

The general hypothesis underlying this paper is that behavior in traditional paradigms of laboratory learning is based on niche-related mechanisms. The specific hypothesis is that the behavior of Norway rats in laboratory mazes is based on niche-related mechanisms related to trail following and navigating. I evaluate seven types of evidence for this hypothesis: (a) resemblance of maze behavior to behavior in unconstrained settings; (b) importance of experimenter tuning of apparatus and procedures; (c) overdetermination of laboratory behavior; (d) reverse-engineering of niche-related mechanisms from laboratory data; (e) prediction of laboratory results from ecological data; (f) contribution of specific relative to general mechanisms; and (g) phylogenetic conservation and ecologically-based convergence and divergence of maze mechanisms. I conclude there is strong evidence for the hypothesis that behavior of rats in laboratory mazes is based on niche-related mechanisms. I suggest that a niche-related approach to laboratory learning paradigms has conceptual generality and the potential to facilitate connections with the study of neurophysiology, genetics, and evolution.

Animals↗
PubMed1997

Determinants of pressure pain threshold in adult twins: evidence that shared environmental influences predominate.

The objective of this study was to examine the relative contribution of genetic and environmental factors in determining pain perception in a classical twin study. Dolorimeter measurements of pressure pain threshold (PPT) were recorded in 609 healthy female-female twin pairs of whom 269 pairs were monozygotic (MZ) and 340 were dizygotic (DZ). There was a strong correlation (R) in PPT in both MZ and DZ pairs (R(MZ) = 0.57, 95% confidence interval (CI): [0.49, 0.65]; R(DZ) = 0.51, 95% CI: [0.42, 0.59]). The slight excess in intraclass correlation observed in MZ when compared with DZ twins corresponds to a heritability for PPT of only 10% and is not statistically significant. Neither estimate of intraclass correlation was substantially altered after adjusting for a range of potential confounding variables including age, current tobacco and alcohol use, current analgesic use, psychological status assessed by the general health questionnaire, and social class. The dolorimeter measurements were shown to be reliable (between observer agreement R = 0.66; within observer agreement R = 0.70-0.76) and stable over time. In conclusion, these data suggest that there is no significant genetic contribution to the strong correlation in PPT that is observed in twin pairs. These findings reinforce the view that learned patterns of behaviour within families are an important determinant of perceived sensitivity to pain.

Adult↗
PubMedDate not supplied

Aluminum effects on operant performance and food motivation of mice.

Previous studies demonstrated better performance of operant tasks in mice fed excess aluminum (Al) in the diet. The current study examined whether (a) Al leads to impairment of spatial alternation after extended practice, (b) Al enhances performance of an operant task that emphasizes motor learning and ability (differential reinforcement of high rates, DRH), and (c) Al enhances food motivation as reflected in progressive ratio (PR) performance. Male Swiss Webster mice were fed purified diets containing 7 (control), 500, or 1000 microg Al/g diet. Subgroups were fed excess Al diets during development (conception to 35 days postnatal) or as adults (35 days postnatal through the end of testing). Operant training and testing were conducted at 50 days postnatal. Data indicated that extended training of developmentally exposed mice did not lead to performance deficits, that DRH performance of both developmentally and adult-exposed mice was enhanced, and that food motivation (PR task) was significantly greater in the adult-exposed group with a similar trend in the developmentally exposed group. Aluminum may bias performance of food-motivated tasks by influencing food motivation.

Aluminum↗
PubMed2002

Impairments of reversal learning and response perseveration after repeated, intermittent cocaine administrations to monkeys.

The current experiments examined the effects of acute or repeated, intermittent administrations of cocaine on the acquisition and reversal of object discriminations by Vervet monkeys in order to test the hypothesis that cocaine treatment affects performance of tasks that depend upon the functions of the orbitofrontal cortex and amygdala. An acute dose of cocaine (1 mg/kg; 20 min prior to testing) impaired reversal of a previously learned object discrimination but had no effect on acquisition of a novel one. Specific impairments of reversal learning were also observed in monkeys 9 and 30 days after repeated administrations of cocaine (2 or 4 mg/kg, once daily for 14 days) that were perseverative in nature, indicating persistent behavioral consequences of repetitive dosing. The results indicate that repeated cocaine administrations produce enduring impairments of object discrimination learning when the inhibition of a previously conditioned response is required. These findings suggest that long-term cocaine administration may disrupt orbitofrontal efferents to the striatum, resulting in impaired inhibition of established conditioned responses.

Animals↗
PubMed2001

Prevalence of atopy and asthma in eastern versus western Europe: why the difference?

LEARNING OBJECTIVES: This article reinforces the reader's knowledge of the epidemiology of allergy and asthma in eastern versus western European countries and the ability to recognize the different hypotheses formulated to explain the rising trend of allergic asthma in Europe. DATA SOURCES: Articles in English comparing the epidemiology of allergy in eastern versus western Europe published before December 31, 2000. RESULTS: Significant higher prevalences of atopy and allergic asthma were observed in the early 1990s among populations living in western compared with eastern European countries. Changes in lifestyle after the fall of the communist system were associated with an increasing trend of atopic sensitization and hay fever in former East Germany after only 6 to 8 years after the Germany reunification. It has been hypothesized that a similar "converging" trend in the prevalence of allergic asthma and of bronchial hyperresponsiveness may take longer periods. CONCLUSIONS: The prevalence of allergic asthma has increased decades earlier in western Europe with respect to eastern Europe. This is probably attributable to changes in lifestyle that had already occurred rather than to air pollution. The factors of a western lifestyle (diet, hygiene, varied allergen exposure) that have determined the difference in allergic asthma prevalence across Europe have yet to be identified.

Asthma↗
PubMed1996

Impaired incentive learning in treated Parkinson's disease.

OBJECTIVE: To quantify the performance of patients with Parkinson's disease (PD) in incentive learning, or learning to respond to stimuli that signal the imminent presentation of a reinforcer, and in paired-associate learning, or learning of word associations. METHODS: The performance of 32 patients with idiopathic PD was compared to that of 25 healthy control subjects, and 32 subjects suffering from arthritis, matched for age and education. The PD and arthritic groups were comparable on a self-report measure of physical disability. All subjects were physically capable of satisfying the contingencies of the incentive learning task. The avoidance task that quantified incentive learning used money loss as an aversive stimulus. The word paired-associate learning task was presented on a computer and feedback was not given on performance. RESULTS: The normal and arthritic groups performed equally well on the avoidance task, whereas the PD group was impaired despite dopaminergic replacement therapy. The groups did not differ significantly in paired-associate learning. CONCLUSIONS: These findings are among the first to suggest that the nigrostriatal dopamine dysfunction associated with PD may play a role in incentive learning but not in paired-associate learning and are consistent with a role for dopamine in certain forms of learning and memory. The findings may highlight differences between tonic and modulated function in the nigrostriatal system.

Aged↗
PubMed1991

Dynamics of time discrimination.

Pigeons tracked sinusoidal sequences of interfood intervals (IFIs) by pausing in each interval for a time proportional to the preceding interval. Schedules with either long (30-90 s) or short (5-15 s) values, with variable numbers of cycles and starting phase each day, were tracked about equally well. Tracking was apparently immediate and did not improve across sessions. Experiment 2, in which long and short series were presented on alternate days, showed that tracking on long was more impaired than on short. Experiment 3 showed that occasional presentation of a short IFI in a series of fixed, longer IFIs caused a reduction in waiting time in the next IFI. These effects are evidence for a fast-acting timing mechanism in which waiting time in the IFI N + 1 is strongly determined by the preceding IFI, N. Earlier IFIs have some cumulative effect, but the details remain to be elucidated.

Animals↗
PubMed2004

Assessments of changes in the effective salience of stimulus elements as a result of stimulus preexposure.

Rats received exposure to 3 flavor compounds, AX and BX, presented in alternation, and CX, presented on a separate block of trials. The hypothesis that this treatment would leave B effectively more salient than C was tested in 3 ways. Experiment 1 showed that the unconditioned response evoked by B was stronger than that evoked by C. Experiment 2 showed that B was more effective than C when used as a reinforcer in a sensory preconditioning procedure. Experiment 3 showed that B was learned about more readily than C as a conditioned stimulus in flavor aversion conditioning. Alternating preexposure to 2 similar stimuli may protect their distinctive features from the loss of salience normally produced by nonreinforced exposure to a stimulus.

Animals↗
PubMed2005

Distinguishing whether dopamine regulates liking, wanting, and/or learning about rewards.

To determine whether dopamine regulates liking, wanting, and/or learning about rewards during goal-directed behavior, the authors tested genetically engineered dopamine-deficient (DD) mice for acquisition of an appetitive T-maze task with and without endogenous dopamine signaling. Experiment 1 established that DD mice treated with L-dihydroxyphenylalanine (L-dopa [LD]) perform similarly to controls on a T-maze task designed to measure liking, wanting, and learning about rewards. Experiment 2, which tested saline-, caffeine-, and LD-treated DD mice on the T maze, separated performance factors from cognitive processes and revealed that dopamine is not necessary for mice to like or learn about rewards but is necessary for mice to seek (want) rewards during goal-directed behavior.

Animals↗

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