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Autism symptoms, including impairments in language development, social interactions, and motor skills, have been difficult to model in rodents. Since children exposed in utero to sodium valproate (VPA) demonstrate behavioral and neuroanatomical abnormalities similar to those seen in autism, the neurodevelopmental effects of this antiepileptic agent were examined in mice following its pre-or postnatal administration. Exposed pups were evaluated in a battery of neurodevelopmental procedures designed to assess VPA-induced retardation (wherein a behavior fails to mature on schedule), regression (wherein a behavior does mature on time but then deteriorates), or intrusions (wherein normal behaviors are overshadowed by stereotypic or self-injurious behaviors). The resulting observations were interpreted in the context of this new strategy to model autism.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.07.006 Byline: Tanya Nekrasova (a), Michelle L. Jobes (b)(c), Jenhao H. Ting (c), George C. Wagner (c), Audrey Minden (a) Keywords: Pak5; Pak6; Knockout mice; Cognitive function; Motor neurons; T-maze; Rotorod test; Open field test; Elevated maze test; Hanging wire test Abstract: PAK6 is a member of the group B family of PAK serine/threonine kinases, and is highly expressed in the brain. The group B PAKs, including PAK4, PAK5, and PAK6, were first identified as effector proteins for the Rho GTPase Cdc42. They have important roles in filopodia formation, the extension of neurons, and cell survival. Pak4 knockout mice die in utero, and the embryos have several abnormalities, including a defect in the development of motor neurons. In contrast, Pak5 knockout mice do not have any noticeable abnormalities. So far nothing is known about the biological function of Pak6. To address this, we have deleted the Pak6 gene in mice. Since Pak6 and Pak5 are both expressed in the brain, we also generated Pak5/Pak6 double knockout mice. These mice were viable and fertile, but had several locomotor and behavioral deficits. Our results indicate that Pak5 and Pak6 together are not required for viability, but are required for a normal level of locomotion and activity as well as for learning and memory. This is consistent with a role for the group B PAKs in the nervous system. Author Affiliation: (a) Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA (b) Joint Graduate Program in Toxicology, Rutgers, The State University of New Jersey, 152 Frelinghuysen Road, Piscataway, NJ 08854, USA (c) Department of Psychology, Rutgers, The State University of New Jersey, 152 Frelinghuysen Road, Piscataway, NJ 08854, USA Article History: Received 10 September 2007; Revised 12 June 2008; Accepted 7 July 2008

The effects of high fat and high carbohydrate diets on alcohol metabolism were studied on blood alcohol and liver fat concentration. In Experiment 1, rats consumed an alcohol-containing liquid diet. Blood was collected for ethanol, glucose and lactate analyses and livers were excised for lipid determination. Blood ethanol and liver fat were lower when rats consumed the high carbohydrate diet. Glucose concentrations were lower in rats fed the high fat diet compared with those fed the high carbohydrate diet when ethanol was consumed. In Experiment 2, rats consumed a high fat, ethanol-containing diet for 13 d. Half of the rats were switched to a high carbohydrate, ethanol-containing diet for an additional 11 d. The same analyses were carried out as for Experiment 1. Switching the high fat-fed rats to the high carbohydrate diet reversed the high blood ethanol and high liver fat values, even though the rats consumed significantly more alcohol with the high carbohydrate diet. In Experiment 3 the same high fat and high carbohydrate diets without ethanol were consumed for 2 wk, at which time ethanol was administered acutely, intraperitoneally, at 2 g/kg. Blood was analyzed for ethanol, glucose and lactate 30, 60 and 120 min after injection. Rats fed the high carbohydrate diet had lower blood ethanol but higher lactate at 120 min compared with those fed the high fat diet. The results suggest that the rate of ethanol elimination is slower in rats fed high fat than in those fed high carbohydrate diets, resulting in elevated blood ethanol and liver fat levels for the former. KEY WORDS: * blood alcohol * blood glucose * blood lactate * liver fat * rats.

The intake of tryptophan decreases the aggressive behavior in rats, and monoaminergic agonist such as tyramine increases the aggression induced by alcohol. Low doses of alcohol cause an increase in offensive or defensive aggression, irrespective of whether the rat is made to eat a diet rich in tryptophan. The serotonergic agonists such as fluoxitine and fenfluramini decrease the aggression caused by alcohol consumption.