Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by defects in communication and social interactions, as well as stereotypic behaviors. Symptoms typically worsen with anxiety and stress. ASD occur in early childhood, often present with regression and have a prevalence of 1 out of 68 children. The lack of distinct pathogenesis or any objective biomarkers or reliable animal models hampers our understanding and treatment of ASD. Neurotensin (NT) and corticotropin-releasing hormone (CRH) are secreted under stress in various tissues, and have proinflammatory actions. We had previously shown that NT augments the ability of CRH to increase mast cell (MC)-dependent skin vascular permeability in rodents. CRH also induced NT receptor gene and protein expression in MCs, which have been implicated in ASD. Here we report that serum of ASD children (4-10 years old) has significantly higher NT and CRH levels as compared with normotypic controls. Moreover, there is a statistically significant correlation between the number of children with gastrointestinal symptoms and high serum NT levels. In Bull Terriers that exhibit a behavioral phenotype similar to the clinical presentation of ASD, NT and CRH levels are also significantly elevated, as compared with unaffected dogs of the same breed. Further investigation of serum NT and CRH, as well as characterization of this putative canine breed could provide useful insights into the pathogenesis, diagnosis and treatment of ASD.

The pharmacokinetics of nalmefene, a new narcotic antagonist which has recently been shown to be effective in the treatment of a stereotypic behavior disorder (crib-biting) in the horse, has been evaluated. Following rapid i.v. injection of a pharmacologically effective dose of 0.4 mg/kg of nalmefene HCl to two crib-biting horses, the plasma concentration - time profile of intact nalmefene declined rapidly in a biexponential manner with a terminal elimination of half-life (t1/2) of approximately 50 min in both animals. Total plasma clearance (CL) and the volume of distribution at steady-state (V(ss)) were 2.8 L/hr/kg and 2.5 L/kg, respectively, indicating high clearance and extensive distribution of the drug. Following i.m. injection of 1 mg/kg of the drug to three other horses, nalmefene had an "apparent" t1/2 of 3 to 5 hr which suggests some form of depot effect or altered disposition occurred via this route of administration. After oral administration of 2 mg/kg of nalmefene, no intact drug could be detected in plasma. However, high plasma concentrations of nalmefene glucuronide appeared rapidly and were detectable for up to 16 hr following administration. The latter observation indicates that nalmefene has poor oral bioavailability in the horse as a result of extensive "first-pass" metabolism and must be administered parenterally for effective control of stereotypic behavior.

Twenty, 6 to 9 kg Yorkshire piglets were used in 2 trials. Ten piglets received an IM injection of naltrexone at a dose of 1 to 1.3 mg/kg. Ten control pigs received saline. Blind behavioral testing in a "squeeze chute" was conducted 40 minutes after injection. The "squeeze chute" consists of two padded plywood panels hinged on a base to form a V. Each pig was squeezed for 60 seconds. After release, eahh pig remained in the padded V for 10 minutes. There was sufficient room for the pigs to walk a few steps. Both naltrexone- and saline-treated pigs eventually crouched down in the chute and relaxed against the padded sites of the V. Naltrexone-pretreated pigs had a longer latency to achieve relaxation—311.8±47.8 seconds vs. 161.8±30.38 seconds (SE) (p<0.02). Each stage of relaxation at induction was rated on a 1–4 scale (1 = squealing and jumping, 4 = relaxed quietly). Naltrexone-treated pigs had significantly lower relaxation ratings than saline-treated pigs (1.90 vs. 3.20) (p<0.01). Treatment had no effect on the final degree of relaxation. Naltrexone partially blocked the relaxation response.