All data are stored in a hard disk of a PC in our laboratory and a back-up copy in also saved in a mobile HD unit
November 17, 2021
All data are stored in a hard disk of a PC in our laboratory and a back-up copy in also saved in a mobile HD unit. in synaptic transmission, neural plasticity and information processing. Prepuberal LP-211 (at lower dose) reduced horizontal activity and (at higher dose) increased SSA, only for NHE but not in NRB rats. Prepuberal LP-211 increased, in NHE rats, L-Glu in the PFC and L-Asp in the VS (at 0.250 mg/kg dose), whereas (at 0.125 mg/kg dose) it decreased L-Glu and L-Asp in the DS. The L-Glu was decreased, at 0.125 mg/kg, only in the VS of NRB rats. The DAT levels were decreased with the 0.125 mg/kg dose (in the PFC), and increased with the 0.250 mg/kg dose (in the VS), significantly for NHE rats. The basal NMDAR1 level was higher in the PFC of NHE than NRB rats; LP-211 treatment (at 0.125 mg/kg dose) decreased NMDAR1 in the VS of NRB rats. This study represents a starting point about the impact of developmental 5-HT7-R activation on neuro-physiology of attentive processes, executive functions and their neural substrates. Introduction The interface between the prefrontal cortex (PFC) and the striata represents the neural substrate for the parallel processing of cognitive and non-cognitive information , . Therefore, this neural site has been the target of neurophysiological and imaging studies in relation to neuropsychiatric problems , . The neurogenetic approach in model systems has been used so far to study complex behaviour ,  and its neural substrates. This approach will likely lead to a better understanding of neuropsychiatric problems such as Attention-Deficit Hyperactivity Disorder (ADHD), Autism, Schizophrenia and Depression. In the mammalian brain, the communication between the PFC and the dorsal/ventral striatum entails the amino acid L-Glutamate (L-Glu) acting through different ionotropic  and metabotropic receptors, Mouse monoclonal to CD152(FITC) transduction mechanisms and various modulators , . The latter include dopamine (DA), norepinephrine (NE), serotonin (5-HT), and histamine. A series of clinical, pharmacological, biochemical and molecular biology studies have supported the dopamine hypothesis in the last fifty years , , which has yielded a wealth of information giving rise to a major knowledge in the field of neurosciences. For instance, in the case of ADHD, DA-ergic psychostimulant drugs like methylphenidate (MPH) and the amphetamines have been largely DAPK Substrate Peptide DAPK Substrate Peptide used. Notwithstanding, the amino acid transmission between the PFC and the striata is usually modulated by 5-HT that is released by axon terminals of raphe nuclei and may operate through seven receptor families. Among these, the 5-HT7 receptor subtype is the target of LP-211, a newly synthesised selective agonist , . It DAPK Substrate Peptide is likely to hypothesise that this receptor could serve a new therapeutic target for ADHD and other neuropsychiatric problems sharing attention deficit. Therefore, in this manuscript we attempt to investigate long-term effects of a prepuberal, subchronic treatment, by LP-211, on adult behaviour, amino acid transmitters and synaptic markers, using a well documented rat model for ADHD . Animal models for studying ADHD can be of genetic and non-genetic type . The Naples High Excitability (NHE) rat is usually a classically validated genetic model, which reproduces the mesocortical variant of ADHD , , , . In particular, their profile is usually characterised by a dysfunctioning mesocortical DA branch with an attention deficit, hyperactivity and altered executive functions. Therefore, adolescent male rats of the Sprague-Dawley-derived NHE collection, and their Naples Random-Bred (NRB) ,  controls, received daily exposure to LP-211 (0.0, 0.125, 0.250 or 0.500 mg/kg), from post-natal DAPK Substrate Peptide day 30C31 to 43C44. By using a multidisciplinary approach, here we show that prepuberal LP-211 yields long lasting changes on adult behaviour, improving spatial attention in a dose dependent manner, associated with altered expression of pre- and post-synaptic markers. The results of the present experiments may represent an important starting point to explore how selective 5-HT7 receptor activation can impact upon the neurophysiology of attentive processes, executive functions and their neural substrates. This may, in turn, lead to a better understanding of developmental neuropsychiatric disorders that share activity, attention and executive function problems. Results Body weight To evaluate possible LP-211 developmental-treatment influences on body growth, the body weight was.