Biomedical subjects

S P Baron

Publications and source records attributed to S P Baron.

7 recordsLinked to original sources

PubMed2001

Mouse strains differ under a simple schedule of operant learning.

Recent advances in understanding the composition of the human and mouse genomes have paved the way to a more detailed understanding of the influence of genes on behavior, particularly learning and memory. One problem with many learning paradigms is the great length of training time required to generate a stable baseline. Our goal for the current studies was to develop a method of rapidly assessing learning and to use it to compare various strains of mice. The acquisition of a simple nose-poke was determined in operant chambers with two nose-poke holes illuminated: a single nose poke in one hole resulted in the presentation of 0.01 ml evaporated milk; responses in the other hole did not result in dipper presentation. All mice of the B6JxImJ F1, C57BL/6J, 129X1/SvJ and C3H/HeJ mice emitted 50 or more correct operant responses, whereas fewer than 50% of 129X1/SvJ and 75-90% of mice of Balb/cByJ, DBA/2J and the outbred CD-1 mice emitted 50 or more correct operant responses. On average, C57BL/6J emitted 50 operative responses in less than 30 min, whereas DBA/2J mice required nearly 1 h to complete 50 operative responses. Other strains performed at intermediate levels. There was no apparent relationship between operant activity and locomotor activity that may have influenced response acquisition. These findings are consistent with those reported using other learning paradigms and provide a rapid method of learning assessment.

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PubMed2001

Effects of drugs of abuse on response accuracy and bias under a delayed matching-to-sample procedure in squirrel monkeys.

The effects on memory of drugs of abuse from several pharmacological classes were examined in four adult male squirrel monkeys responding under a delayed matching-to-sample schedule of food presentation. Subjects were required to emit 20 responses on a sample key transilluminated by either a constant white or a flashing blue light. The twentieth response initiated a 3-second delay followed by presentation of two comparison stimuli. If a response was made to the key that matched the sample stimulus (correct match), a single food pellet (97 mg) was delivered. Pentobarbital (0.32-10 mg/kg), diazepam (0.1-5.6 mg/kg), phencyclidine (0.01-0.32 mg/kg) and cocaine (0.1-3.2 mg/kg) dose-dependently reduced accuracy of matching performance towards chance levels. Amphetamine (0.01-1.0 mg/kg) resulted in a small, but statistically significant, reduction in accuracy at a dose of 0.56 mg/kg, while 1.0 mg/kg completely suppressed responding. Analyses indicated that pentobarbital, diazepam and cocaine produced either position or color biases in responding, and in some cases these biases in responding were associated with decreases in accuracy. No such response biases were observed with phencyclidine or D-amphetamine. These results suggest that drug effects on working memory performance can, in some cases, be the result of non-mnemonic processes. Thus, they illustrate the importance of examining behavioral endpoints in addition to task accuracy when interpreting drug effects on working memory in laboratory animals.

Animals↗

PubMed1998

Effects of drugs of abuse and scopolamine on memory in rats: delayed spatial alternation and matching to position.

Drugs of abuse produce amnestic effects in humans and laboratory animals in a variety of tasks. Generally, only a few compounds have been examined in any particular procedure. It was the goal of the present studies to examine drugs of abuse of different pharmacological classes in rats responding under two behavioral schedules historically employed as experimental models of memory: spatial alternation and matching to position. One group of rats responded under a single-response spatial-alternation baseline with a 10-s delay and another group responded under a matching-to-position baseline with delay values of 3, 10 and 30 s. Performance under the spatial-alternation baseline was characterized by low variability and >90% accuracy. Under the matching-to-position baseline, saline control percent accuracy was >95% at 3 s, >85% at 10 s and >70% at 30 s. Under spatial alternation cocaine, d-amphetamine, pentobarbital, diazepam, phencyclidine, scopolamine and methscopolamine produced significant (P<0.05) effects on accuracy, whereas only cocaine, d-amphetamine, pentobarbital and phencyclidine disrupted accuracy under the matching-to-position baseline. These results suggest that spatial alternation may be a more sensitive baseline for determining drug effects on working memory in the rat.

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PubMed1995

Competitive and uncompetitive N-methyl-D-aspartate antagonist discriminations in pigeons: CGS 19755 and phencyclidine.

The purpose of the present studies was to examine representative uncompetitive and competitive NMDA antagonists, as well as the glycine/NMDA antagonist, HA 966, in pigeons trained to discriminate either PCP or CGS 19755 from saline. Separate groups of pigeons were trained to discriminate either the uncompetitive, phencyclidine (PCP; 0.32 and 1.0 mg/kg, IM), or the competitive, CGS 19755 (cis-4-phosphonomethyl-2-piperidine-carboxylic acid; 1.8 mg/kg, IM), NMDA antagonists from saline. Uncompetitive and competitive NMDA antagonists were examined in generalization studies, as were the racemate and the (+) and (-) stereoisomers of HA 966 (3-amino-1-hydroxypyrrolid-2-one). Dizocilpine (MK 801) was fully generalized to PCP but not to CGS 19755. All competitive NMDA antagonists tested were fully generalized to CGS 19755, but not to PCP. The competitive antagonists, however, produced > 50% PCP-appropriate responding. The (+) isomer of HA 966 was fully generalized by three of four pigeons discriminating PCP (1.0 mg/kg) or CGS 19755, whereas the racemate and the (-) isomer produced < 40% drug-appropriate responding in either group. Neither NMDA, morphine, nor pentobarbital produced > 10% drug-appropriate responding in either discrimination group. The competitive antagonists tended to produce peak drug-appropriate responding at times greater than 60 min after administration, whereas uncompetitive antagonists produced peak drug-appropriate responding at earlier times. HA 966 also had a relatively slow onset of action as compared to PCP. These results suggest that antagonists acting at different modulatory sites of the NMDA receptor complex produce similar, but not identical, discriminative stimuli.

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PubMed1993

Dipsogenic effects of excitatory amino acid agonists in pigeons.

Three excitatory amino acid agonists [N-methyl-D-aspartate (NMDA), kainate and alpha-amino-2,3-dihyro-5-methyl-3-oxo-4-isoxalzolepropanoic acid], each selective for separate glutamate binding sites, were evaluated for dipsogenic responses in pigeons. NMDA and kainate produced a reliable and rapid drinking response (up to 30% of body weight over 3 hr). alpha-amino-2,3-dihyro-5-methyl-3-oxo-4-isoxalzolepropanoic acid, up to doses which produced profound effects on motor behavior (18.0 mg/kg i.m.), did not produce a reliable drinking response. The dipsogenic effects of NMDA and its stereoisomer, N-methyl-L-aspartate, were antagonized by the competitive NMDA antagonist, cis-4-(phosphonomethyl)-2-piperidinecarboxylic acid. cis-4-(phosphonomethyl)-2-Piperidinecarboxylic acid failed to prevent drinking produced by kainate or water deprivation. These results suggest that NMDA-, kainate- and water deprivation-induced drinking are mediated via separate mechanisms and that NMDA induced drinking is mediated via NMDA receptors.

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PubMed1988

Effects of selection delays on radial maze performance: acquisition and effects of scopolamine.

The effects of post-selection confinement (delays) on both the acquisition of performance and the response to the muscarinic blocker, scopolamine, were examined in an automated version of the eight arm radial maze. Long-Evans rats, exposed to post-selection delays of 0.5 sec (n = 4) or 100 sec (n = 4) during daily training trials did not differ in either the number of trials to acquire an accurate baseline of performance or in the amount of time required to obtain all eight food pellets. However, the pattern (delta-arm scores) of within-session arm selections demonstrated by the two groups of rats differed. Rats exposed to the 0.5-sec delay typically selected arms adjacent to arms from which they exited while rats exposed to the 100-sec delay were more likely to enter arms 2-removed from the exit arm. When scopolamine (0.03 to 1.0 mg/kg) was administered prior to testing, rats in the 100-sec delay group showed a greater reduction of accuracy and a larger increase in selection latency than rats in the 0.5-sec delay group. The differential effect of delay value on delta-arm scores was also eliminated in a dosage dependent manner with scopolamine. Scopolamine methylbromide (0.3 mg/kg) was found to have little effect on performance. In summary, the results indicate that the post-selection delay procedure is a sensitive and selective test for chemical-induced dysfunctioning of spatial memory in rats.

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PubMed1988

Effects of scopolamine on repeated acquisition of radial-arm maze performance by rats.

Rats repeatedly acquired the performance of selecting only the four baited arms in an automated eight-arm radial maze, with the arms containing food pellets randomly assigned prior to each session. During each 14-trial (trial: obtain all four pellets) daily session, the number of errors (selecting nonbaited arms or repeating arm selections) showed a within-session decline, and choice accuracy for the first four arm selections showed a positive acceleration across trials for all rats. An index-of-curvature statistic, calculated for total errors, was used to quantify both the within- and between-session improvement of performance. Scopolamine (0.03 to 0.3 mg/kg, ip), but not methylscopolamine (0.3 mg/kg), reduced the accuracy of the first four selections of each trial and increased total within-session errors for all rats. Session times also were increased by scopolamine. An examination of within-session accuracy showed only slight signs of improvement at the higher dosages of scopolamine. The results indicate that behavior in transition states maintained by reinforcement contingencies in the radial maze is similar to that maintained by extended chained schedules, despite the fact that some of the stimuli controlling behavior in the maze are absent at the moment behavior is emitted.

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