Autism spectrum disorders (ASDs) are heterogenous neurodevelopmental disorders characterized by impairment in social, communication skills and stereotype behaviors. While autism may be uniquely human, there are behavioral characteristics in ASDs that can be mimicked using animal models. We used the BTBR T+tf/J mice that have been shown to exhibit autism-like behavioral phenotypes to 1). Evaluate cannabinoid-induced behavioral changes using forced swim test (FST) and spontaneous wheel running (SWR) activity and 2). Determine the behavioral and neurochemical changes after the administration of MDMA (20 mg/kg), methamphetamine (10 mg/kg) or MPTP (20 mg/kg). We found that the BTBR mice exhibited an enhanced basal spontaneous locomotor behavior in the SWR test and a reduced depressogenic profile. These responses appeared to be enhanced by the prototypic cannabinoid, Δ9-THC. MDMA and MPTP at the doses used did not modify SWR behavior in the BTBR mice whereas MPTP reduced SWR activity in the control CB57BL/6J mice. In the hippocampus, striatum and frontal cortex, the levels of DA and 5-HT and their metabolites were differentially altered in the BTBR and C57BL/6J mice. Our data provides a basis for further studies in evaluating the role of the cannabinoid and monoaminergic systems in the etiology of ASDs.

Dichlorvos (O,O-dimethyl-2:2-dichlorovinyl phosphate) was administered IP (3 mg/kg) daily for 10 days to a group of albino rats. Open field behavior was significantly depressed below the mean of the control group. On day 7, ambulation was reduced to 24% of the mean but recovered to 60% on day 10. Similarly, rearing response was decreased on day 7 and showed a fast recovery on day 10 but the preening response further declined on day 10. Defecation, on the contrary, was suppressed to 0% on day 7 and showed complete recovery on day 10. Motor activity showed a significant depression and fine movements were reduced more than gross movements in the second phase. Dopamine was significantly decreased on days 5 and 7 but showed a 13% recovery in the brain stem on day 10. Norepinephrine was significantly reduced in the cerebral hemisphere while serotonin was decreased both in cerebral hemisphere and brain stem. Neither of thse two amines showed significant recovery on day 10. Interesting concordance of the open field behavioral changes with the levels of dopamine, norepinephrine, and serotonin in the various regions of the rat brain was noticeable and has been discussed.

Two-month-old male B/6C3F1 mice were treated for 10 weeks with 100 microM aluminum lactate (Al) in drinking water. This dose of Al did not alter body weight, and there was no evidence of systemic toxicity. The degree of phosphorylation of several kinases which lead to transcription factor activation (reflecting the extent of their activation) was studied. The proportion of extracellular signal-regulated kinase (ERK) that was activated was depressed in cortex but not in the hippocampus following treatment but c-Jun N-terminal kinase (JNK), p38, IkappaB phosphorylation was unaltered in either tissue. Treatment of mice with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) alone produced no significant changes in the degree of activation of any transcription factor studied. When MPTP dosing had been preceded by extended exposure to low levels of Al in drinking water, ERK activation was profoundly depressed in cortex and hippocampus, whereas JNK in hippocampus and IkappaB in cortex were greatly elevated. These changes consequent to exposure to both Al and MPTP were accompanied by an increase in NF-kappaB in both regions, whereas AP-1 was elevated in the hippocampus alone. Neither agent alone modulated AP-1 or NF-kappaB. Thus a synergistic interaction occurred between the toxicants. This interaction tended to promote the functioning of a kinase largely associated with inflammation and to depress that of ERK, which is associated with maintenance of cell survival. It is concluded that exposure to levels of Al with no evident toxicity can worsen the response to an acute challenge with MPTP. Al treatment alone was able to increase striatal 3,4-dihydroxyphenylacetic acid levels, suggesting an elevation of the rate of dopamine turnover in the striatum. However, no interaction in alteration of monoamine levels was found between Al and MPTP.

Play behaviours are exhibited by many mammalian species. The similarity of such behaviour across children, non-human primates and rats makes it an especially appropriate target for the investigation of drug- or toxicant-induced disruption. In this study the acute effects of cocaine on play behaviour in male and female Sprague-Dawley rats was assessed. Same-sex dyads of rats (postnatal day 35-36) were separated 24 h prior to testing. On the following day, one or both rats of the dyad were injected with the same dose of cocaine (0, 2.5, 5.0 or 20.00 mg/kg). Thirty minutes later the rats were placed together and, after 5 min of habituation, the frequency of pins and crawl-overs were measured for each subject. In dyads in which both rats were treated, crawl-overs and pinning behaviour were decreased by 20 mg/kg cocaine. In dyads in which only one rat was treated, there was marginal effect of cocaine treatment on pinning frequency, while crawl-overs were unaffected. Pinning frequency was not sexually dimorphic in either type of dyad; however, crawl-overs were more frequently exhibited by females in dyads in which only one rat was treated. Thus, pinning behaviour in juvenile rats appears somewhat more sensitive to cocaine-induced disruption than crawl-over behaviours. Additionally, the presence of an untreated rat appears to attenuate the play-disrupting effects of cocaine on pinning frequency.