Neurobiologia e terapia dei disturbi della sfera affettiva nell'autismo: conoscenze attuali

L’autismo è un disordine dello sviluppo del cervello che insorge in periodo perinatale ed è caratterizzato da disturbi del comportamento sociale, da difficoltà nelle interazioni con gli altri, da deficit del linguaggio, dalla presenza di atteggiamenti di tipo ripetitivo ed ossessivo, da alterazioni della sfera affettiva ed emozionale. L’incidenza dell’autismo ha ormai assunto le dimensioni di una vera e propria epidemia, per cui è prioritario avere a disposizione terapie realmente efficaci. Purtroppo attualmente non esiste alcun trattamento farmacologico che non sia puramente sintomatico. La carenza di farmaci efficaci è dovuto al fatto che i meccanismi neurobiologici alla base dell’autismo sono ancora poco conosciuti, e di conseguenza è particolarmente diff i c i l e ottenere farmaci che diano risultati soddisfacenti. Tuttavia, nel corso degli ultimi anni sono stati compiuti importanti progressi sui vari aspetti anatomici e funzionali del cervello dei soggetti autistici, che hanno permesso di comprendere, almeno in parte, i meccanismi neurobiologici che sono alla base di tale patologia. In questa breve rassegna sono analizzate le principali alterazioni neurobiologiche implicate nell’autismo ed i farmaci, anche se con modesti risultati, impiegati nella sua terapia.Autism is a disorder affecting the brain. It comes out in the prenatal period and is characterized by disorders of social behaviour, communicative difficulties, socialization, language, presence of obsessive and repetitive habits and disorders of the emotional field. It is a real epidemic, so we need to have real effective therapies for it. Unfortunately there are no pharmaco - logical treatments at the moment. This is due to the fact that neurobiological mechanisms of autism are still unknown, so it is difficult to obtain specific drugs for it. Nevertheless, over these last years important progresses have been made over the study of anatomic and functional brain aspects. These studies allowed us to understand, in part, the neurobiological mecha - nisms of this pathology. In the following report we have analy - zed the most important neurobiological alterations involved in autism and related drug therapy

Perinatal exposure to 5-metoxytryptamine, behavioural-stress reactivity and functional response of 5-HT1A receptors in the adolescent rat

Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5- metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these experimental models, and by the co-administration of the selective and silent 5-HT1A antagonist WAY 100635. Results indicate that a single daily injection of 5MT to, pregnant dams from gestational days 12 to 21 (1 mg/kg s.c.), and to the pups from postnatal days 2 to 18 (0.5 mg kg s.c.), induce in the adolescent rat offspring: an increase in the percentage of entries and time spent on the open arms in the elevated plus maze; a reduction in locomotor activity and rearing frequency, and an increase in the time spent on the central areas in the open field test; a decrease in immobility and an increase in swimming in the forced swim test. Acute administration of LY 228729 (1.5 mg/kg s.c.) strongly decreases rearing frequency and increases peripheral activity in the open field test, and decreases immobility and increases swimming in the forced swim test both in perinatally vehicle and 5MT-exposed offspring. Co-administration of WAY 100635 (0.25 mg/kg s.c.) abolishes the effects exerted by LY 228729. These results suggest that, in the adolescent rat, perinatal exposure to 5MT enhances the stress-related adaptive behavioural responses, presumably through a predominant action on presynaptic 5-HT1A receptors and does not deteriorate the functional response of 5-HT1A receptors to selective agonist and antagonist compounds

Effects of pre- and postnatal exposure to 5-methoxytryptamine and early handling on an object-place association learning task in adolescent rat offspring.

A reduction in 5-HT1A receptor response enhances learning and memory performance in rats. Pre- and postnatal treatment with 5-methoxytryptamine (5MT), a non-selective serotonergic agonist, and early handling, reduce the number of 5-HT1A receptors in neonatal and pre-pubertal rat progeny. The aim of this study was to investigate in adolescent male rats the consequences of pre- and postnatal treatment with 5MT and its interaction with early handling on an object-place association learning task, the "Can test", a motivated, non-aversive, spatial/object discrimination task. Results show that a single daily injection of 5MT from gestational days 12 to 21 (1 mg/kg s.c.) and from postnatal days 2 to 18 to pups (0.5 mg/kg s.c.), increases the level of activity and the number of correct responses, and decreases the number of reference memory errors in the progeny as adolescent, compared to vehicle-treated rats. Similar effects are observed following a daily, brief, maternal separation of the pups from postnatal days 2 until 21. Furthermore, when 5MT-treated rats underwent to early handling procedure, the effects induced by 5MT increased handling-induced facilitation of the object-place association. These results suggest that pre- and postnatal treatment with 5MT enhances learning in the "Can test", probably due to a reduction in 5-HT1A receptors in the hippocampus. Whether the potentiation exerted by pre- and postnatal 5MT on early handling effects may be related to a further damping of 5-HT1A receptor response is not yet assessed; however, our data demonstrate that this association is able to induce long-term facilitative effects on spatial learning performance in a non-aversive spatial/object discrimination task in the adolescent rat offsprin