Aniracetam improves contextual fear conditioning and increases hippocampal gamma-PKC activation in DBA/2J mice.

DBA/2J (D2) mice display poor contextual learning and have less membrane-bound hippocampal protein kinase C (PKC) compared with C57BL/6 (B6) mice. Aniracetam and oxiracetam were previously shown to improve contextual learning in D2 mice and increase PKC activity. This study investigated a possible mechanism for learning enhancement by examining the effects of aniracetam on contextual fear conditioning and activation of the y isoform of PKC (gamma-PKC) in male D2 mice.

Quantitative genetics and mouse behavior.

Quantitative differences are observed for most complex behavioral and pharmacological traits within any population. Both environmental and genetic influences regulate such individual differences. The mouse has proven to be a superb model in which to investigate the genetic basis for quantitative differences in complex behaviors.

Solubilization of benzodiazepine receptors from long- and short-sleep mice.

Previous studies have shown that long-sleep (LS) and short-sleep (SS) mice, which were selectively bred for differential responses to the sedative-hypnotic actions of ethanol, also differ in response to several other agents that act at the GABAergic receptor. Binding at cortical benzodiazepine receptors is enhanced differentially by GABA and ethanol in membranes prepared from the two lines of mice with SS receptors enhanced to a greater extent. Heat denaturation studies and other biochemical characterizations of these receptors suggest that the GABAergic receptor complex from the two lines of mice differs.

Genetic selections for nicotine and cocaine sensitivity in mice.

We are using selective breeding to develop lines of mice which differ maximally in their responses to nicotine, and independent lines of mice which differ maximally in their responses to cocaine. The foundation population was the genetically heterogeneous HS mice. On day 1, baseline (saline injected) activity of each mouse was measured in an automated Y-maze over 3 minutes.

Variation of nicotinic binding sites among inbred strains.

The specific binding of L-nicotine and alpha-bungarotoxin, two ligands which label different populations of putative nicotinic receptors, was determined in eight brain regions of 19 inbred mouse strains. The dissociation constants for L-nicotine (average = 2.26 nM) and alpha-bungarotoxin (average = 0.

Genetic influences on nicotine responses.

Male mice from 19 inbred strains were tested for the effects of nicotine on six responses: respiratory rate, acoustic startle response, Y-maze crosses, Y-maze rears, heart rate and body temperature. Dose-response curves were constructed for each strain on each test in a multitest battery. Results indicated that the responses were strongly influenced by the genotype of the animal.

Long-term repeatability of human alcohol metabolism, sensitivity and acute tolerance.

Thirty-eight subjects in the Colorado Alcohol Research on Twins and Adoptees (CARTA) were brought back between 3 and 39 months after their initial testing to be retested on a shortened version of the standard CARTA procedures. As before, subjects were given a dose of ethanol (0.8 g/kg) calculated to bring their blood alcohol level (BAL) to near 100 mg/dl, but no topping doses were administered in the retests to maintain BALs near peak for 3 hours, as was done previously.

Behavioral desensitization to nicotine is enhanced differentially by ethanol in long-sleep and short-sleep mice.

In order to assess the anticonvulsant potency of ethanol, male and female long-sleep (LS) and short-sleep (SS) mice were pretreated with ethanol 7.5 min prior to challenge with an ED80 dose of nicotine (LS: 4.25 mg/kg; SS: 6.