LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT2A receptor

Compounds that activate the 5-HT2A receptor, such as lysergic acid diethylamide (LSD), act as hallucinogens in humans. One notable exception is the LSD congener lisuride, which does not have hallucinogenic effects in humans even though it is a potent 5-HT2A agonist. LSD and other hallucinogens have been shown to disrupt prepulse inhibition (PPI), an operational measure of sensorimotor gating, by activating 5-HT2A receptors in rats. We tested whether lisuride disrupts PPI in male Sprague–Dawley rats. Experiments were also conducted to identify the mechanism(s) responsible for the effect of lisuride on PPI and to compare the effects of lisuride to those of LSD. Confirming a previous report, LSD (0.05, 0.1, and 0.2 mg/kg, s.c.) reduced PPI, and the effect of LSD was blocked by pretreatment with the selective 5-HT2A antagonist MDL 11,939. Administration of lisuride (0.0375, 0.075, and 0.15 mg/kg, s.c.) also reduced PPI. However, the PPI disruption induced by lisuride (0.075 mg/kg) was not blocked by pretreatment with MDL 11,939 or the selective 5-HT1A antagonist WAY-100635 but was prevented by pretreatment with the selective dopamine D2/D3 receptor antagonist raclopride (0.1 mg/kg, s.c). The effect of LSD on PPI is mediated by the 5-HT2A receptor, whereas activation of the 5-HT2A receptor does not appear to contribute to the effect of lisuride on PPI. These findings demonstrate that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of lisuride as a non-hallucinogenic 5-HT2A agonist

Autism spectrum disorder severity as a predictor of Battelle Developmental Inventory – Second Edition (BDI-2) scores in toddlers

OBJECTIVE: The study aimed to evaluate the relationship between the severity of autism spectrum disorder (ASD) symptomology and scores on the Battelle Developmental Inventory, Second Edition (BDI-2) in toddlers (n = 325). METHODS: Total scores on the BDI-2 and individual domain scores were examined to explore the relationship between severity of ASD and developmental quotient, impairment in personal-social skills, adaptive functioning, cognition, and communication. RESULTS: Regression analyses controlled for the impact of age and IQ on results, indicating that higher autism severity scores were associated with overall greater impairment and in the total scores and the individual domains of the BDI-2. The domains were found to be differentially affected by severity of ASD. CONCLUSION: These findings suggest severity of ASD may influence symptom presentation. Clinical implications of study findings are discussed