Biomedical subjects

Galen R Wenger

Publications and source records attributed to Galen R Wenger.

5 recordsLinked to original sources

PubMed2005

Working memory in the Ts65Dn mouse, a model for Down syndrome.

This study used a matching-to-position schedule of reinforcement to examine working memory in Ts65Dn and littermate control mice. Initially there appeared to be a memory deficit in the Ts65Dn mice, which disappeared with extended practice. Thus, what appeared as a memory deficit may actually be the result of a delay in learning the concept of matching. These results suggest that delayed learning may be an important factor in other procedures examining working memory in Ts65Dn mice and have important implications for clinical treatment of Down syndrome patients.

Animals↗

PubMed2004

Operant conditioning in the Ts65Dn mouse: learning.

Ts65Dn and littermate controls were trained to respond (nose-poke) under operant schedules of reinforcement. A small difference was observed in the initial operant training of the Ts65Dn mouse that disappeared with training under a fixed-ratio 15 schedule of milk presentation. No difference was observed in a position reversal task in which mice initially trained to respond upon one photocell had to learn to respond on a previously inactive photocell. Under an incremental repeated acquisition of behavioral chains schedule, no difference was observed when one or two responses were required to complete the sequence. However, when three or four responses were required to complete the sequence, a marked deficit was observed in the Ts65Dn mice. These results show that both Ts65Dn and littermate controls can be trained to respond under operant schedules of reinforcement, but that Ts65Dn mice have a learning deficit that is correlated with task difficulty.

Animals↗

PubMed2003

Behavioral training increases local astrocytic metabolic activity but does not alter outcome of mild transient ischemia.

Functional neurological outcome after transient ischemia might be improved by timely therapeutic intervention. To determine if restorative behavioral therapy influences damage, improves task learning, or alters astrocyte metabolic activity after ischemia, rats (food-restricted to 85% of free-feeding weight) were (a) first trained to respond on one of two levers under a fixed-ratio 20 schedule of food presentation (FR20), then (b) subjected to sham manipulation of carotid arteries or 10 min ischemia by four-vessel occlusion, followed by (c) 4 days of operant testing or inactivity, (d) then all rats were tested under a FR20 lever reversal task for 4 weeks, and (e) 3 days after the last behavioral session astrocyte metabolism was assayed by local uptake of [2-14C]acetate. Mild loss of hippocampal neurons occurred in ischemic rats with or without training after ischemia. Glial fibrillary acidic protein-positive astrocytes were present in similar numbers throughout brains of sham control and ischemic rats. Mild ischemia did not impair learning, and no changes in FR20 reversal learning were detected in sham vs. ischemic rats. Net [14C]acetate uptake was unaffected by ischemia but [14C]acetate uptake increased 15-24% (P<0.05; n=12-15/group) in specific structures (caudate, primary motor and sensorimotor cortex, CA1 hippocampus, subcortical white matter) in the pooled groups of rats that had 4 days FR20 testing vs. inactivity before reversal learning. 'Behavioral therapy' (operant testing on the 4 days immediately following either sham manipulation or ischemia) did not alter ischemic outcome, but was associated with higher acetate utilization in regions involved in motor activities.

Acetic Acid↗

PubMed2002

Effect of pentobarbital, d-amphetamine, and nicotine on two models of sustained attention in pigeons.

RATIONALE: The animal literature examining the effects of drugs of abuse on sustained attention has provided conflicting results. One reason for these inconsistencies could be the different type of tasks used to measure sustained attention. OBJECTIVE: Acute effects of pentobarbital (0.3, 1, 3, 5.6, 10, and 13 mg/kg), d-amphetamine (0.03, 0.1, 0.3, 1, 3, and 5.6 mg/kg), and nicotine (0.03, 0.1, 0.3, 1, and 3 mg/kg) were compared in two models of sustained attention. METHODS: Dose-response curves were compared in eight male, white Carneaux pigeons trained under a continuous-trial attention procedure and in six male, white Carneaux pigeons trained under a discrete-trial attention procedure. Both procedures required subjects to respond to a variable and brief signal presentation (signal was presented on average every 6.5 s). RESULTS: Under the continuous-trial procedure, pentobarbital decreased hits as well as increased the number of false alarms and misses at doses that did not impair the ability of the animals to respond. d-Amphetamine and nicotine dose dependently decreased hits and increased misses at doses that did not impair rates of responding. However, neither psychomotor stimulant caused a significant increase in false alarms. Under the discrete-trial procedure, pentobarbital, d-amphetamine, and nicotine decreased hits and correct rejections and increased misses and errors of omission. For the most part, these drug effects occurred at doses that increased the latencies of the animals to respond. When comparing drug effects between the continuous- and discrete-trial procedures, a difference in the false alarm rate was observed. CONCLUSIONS: The present study shows that the continuous-trial procedure was able to detect differences between drug classes that were not apparent under the discrete-trial procedure. Although the lack of a true measure of a false alarm rate continues to be a problem with the continuous-trial procedure, it may be an important procedure for studying the effects of pharmacological agents.

Adrenergic Agents↗

PubMed2002

A single dose of monoclonal anti-phencyclidine IgG offers long-term reductions in phencyclidine behavioral effects in rats.

These studies tested the hypothesis that a single dose of high-affinity anti-phencyclidine monoclonal antibody (anti-PCP mAb) provides long-term protection against behavioral effects of repeated PCP administration in rats. Rats were treated with saline, nonspecific bovine IgG (NS-IgG), or anti-PCP mAb (1.0 g/kg). The next morning, the rats were challenged with escalating i.v. doses of PCP (0.32, 0.56, and 1.0 mg/kg) at 90-min intervals. This regimen was repeated every 3 days for 2 weeks. In the saline and NS-IgG control groups, PCP yielded reproducible and linear dose-dependent effects that remained constant during the experiment. In contrast, the anti-PCP mAb treatment blocked PCP effects on day 1, and sustained significant (P < 0.05) reductions in drug effects for the entire 2-week experiment. Brain PCP concentrations (determined at study termination) were reduced by ~55%, whereas serum concentrations were increased over 4000% compared with controls. Thus, a single dose of antibody medication provided long-term reductions in drug effects and brain concentrations, beyond the expected capacity of the drug-antibody interaction. These data challenge current concepts about in vivo dose dependence and unimolecular interaction between antibody binding sites and small molecules and establish that neuroprotection by mAbs may have an unique mechanism of action.

Animals↗