Biomedical subjects

Adolfo G Sadile

Publications and source records attributed to Adolfo G Sadile.

6 recordsLinked to original sources

PubMed2006

Differential alcohol drinking behaviour and dependence in the Naples low- and high-excitability rat lines.

Alcoholism is composed of a series of phenomena, which can be approached in model systems. Our aim was to investigate psychogenetics of alcohol drinking behaviour and dependence in the Naples rat lines. Thus, adult male rats of the Naples low- (NLE), high-excitability (NHE) and random-bred control (NRB) lines had 24-h access to a four-bottle system with tap water and 5, 10 and 20% alcohol solutions. Total voluntary alcohol intake and preference were measured during a 6-week period. In order to analyze behavioural dependence, two abstinence periods were introduced, followed by re-exposure to the bottles. The first was a pure re-test and the second was a quinine test (adding 0.02% quinine alcohol solution). Finally, to verify the role of opioids on alcohol drinking behaviour, rats received naltrexone (5 mg/kg i.p.). Thirty minutes later, they had access for 2 h to a three-bottle system with water, 5 and 20% alcohol solution, respectively. Results indicate that (i) total alcohol intake on day 1 was higher in both NLE/NHE, becoming higher in NLE rats during the 6-week period, (ii) different alcohol preference patterns in the Naples lines were observed over time of testing, (iii) during re-test, NLE rats showed neither reversibility nor alcohol deprivation effect, (iv) during quinine test, only NLE rats reduced alcohol intake to a lower extent and (v) naltrexone reduced by 50% the intake of the preferred solution. Therefore, the NLE rats appear as a new model for studying the neural substrates of the dependence behaviour.

Alcohol Drinking↗

PubMed2005

The control of responsiveness in ADHD by catecholamines: evidence for dopaminergic, noradrenergic and interactive roles.

We explore the neurobiological bases of attention deficit hyperactivity disorder (ADHD) from the viewpoint of the neurochemistry and psychopharmacology of the catecholamine-based behavioural systems. The contributions of dopamine (DA) and noradrenaline (NA) neurotransmission to the motor and cognitive symptoms of ADHD (e.g. hyperactivity, variable and impulsive responses) are studied in rodent and primate models. These models represent elements of the behavioural units observed in subjects with ADHD clinically, or in laboratory settings (e.g. locomotion, changed sensitivity/responsivity to novelty/reinforcement and measures of executive processing). In particular, the models selected emphasize traits that are strongly influenced by mesocorticolimbic DA in the spontaneously hypertensive (SHR) and the Naples high excitability (NHE) rat lines. In this context, the mode of action of methylphenidate treatment is discussed. We also describe current views on the altered control by mesolimbic catecholamines of appropriate and inappropriate goal-directed behaviour, and the tolerance or intolerance of delayed reinforcement in ADHD children and animal models. Recent insights into the previously underestimated role of the NA system in the control of mesocortical DA function, and the frontal role in processing information are elaborated.

Animals↗

PubMed2003

Dopamine phenotype and behaviour in animal models: in relation to attention deficit hyperactivity disorder.

The phenotypic expression of behaviour is the outcome of interacting neuronal networks and is modulated by different subcortical systems. In the present paper the role of a major subcortical neurochemical system, dopamine (DA), is reviewed. In particular, knockout (KO) technology has given an overwhelming insight into the effects of specific component of the dopaminergic system. Therefore, the behavioural profile of dopamine transporter (DAT), tyrosine hydroxylase (TH), DA and cAMP-regulated phosphoprotein (DARPP 32), and D1, D2, D3, D4 and D5 dopamine receptors knockouts (and their combination) is reviewed.TH, D1, D2, D4 KO mice exhibit decreased locomotor activity, perhaps due to decreased motivational level. D3 KO and DAT KO mice show an increase in basal and novelty-induced activity respectively. It is possible that the increased dopamine levels in DAT KO mice enhance motivation. These observations support the hyperDA hypothesis in hyperactive phenotypes. Moreover, they suggest that the inhibitory effect of psychostimulant drugs, such as methylphenidate and amphetamines, in Attention Deficit Hyperactivity Disorder may be the outcome of an altered balance between auto- and hetero-receptors. However, since KO technology is hampered by blockade of the target at early stages of development, some alternatives have been proposed, such as inducible mutagenesis and inhibitory small RNAs conveyed to target by viral vectors in adulthood.

Animals↗

PubMed2003

Behavioural, pharmacological, morpho-functional molecular studies reveal a hyperfunctioning mesocortical dopamine system in an animal model of attention deficit and hyperactivity disorder.

Clinical and experimental evidence suggest an involvement of dopamine systems, mainly the mesocorticolimbic one (MCL), in Attention-Deficit Hyperactivity Disorder (ADHD). However, it remains to be ascertained whether the systems are hyper- or hypo-functioning, for the implications of the functional state. Indeed, differential functional states of the MCL branches are suggested to be the neural substrate of different ADHD variants. This review covers published and unpublished data from the Naples-High Excitability (NHE) rat, an animal model of ADHD, featuring its main aspects, with no hypertension. Therefore, a multiple approach based on morphological studies of dopamine, norepinephrine, glutamate, acetylcholine and GABA systems, synaptic (Calcium/Calmodulin kinase II) and extrasynaptic (chondroitin sulphates) environments, and molecular biology and pharmacological studies on the dopamine system has been carried out. Morphological findings suggest dopamine neurons in the Ventral Tegmental Area (VTA) to be hypertrophic in NHE rats. The mesostriatal and mesolimbic dopamine branches appear to be normal in basal conditions. However, the striatal interface is probably defective following activation. Conversely, the prefrontal cortex, which represents the second main target of VTA dopamine neurons, has many alterations at the basal level. Therefore, the emerging picture is the association of a hyperinnervating and hyperfunctioning mesocortical branch of the dopamine system. Thus, the evidence gathered so far might improve our understanding of the neural substrates of neuropsychiatric disorders such as ADHD, schizophrenia and drug addiction.

Animals↗

PubMed2002

A morphometric evidence for a hyperfunctioning mesolimbic system in an animal model of ADHD.

The hyperfunctioning dopamine hypothesis in the mesocorticolimbic (MCL) system has been addressed by a neurogenetic approach in model systems. Thus, a morphometric analysis was carried out on neurons of origin of Substantia Nigra (SN) and Ventral Tegmental Area (VTA) dopamine systems of the Naples High-Excitability (NHE), Low-Excitability (NLE) and control lines. Male adult rats were tested in a spatial novelty for indices of activity and non-selective attention. Mesencephalic coronal sections were processed for tyrosine hydroxylase (TH) immunohistochemistry and cytochromoxidase (C.O.) histochemistry. Image analysis in the rostro-caudal plane showed (i) a higher neuron size of TH+ elements in the VTA of NHE and NLE, across the entire structure in the NHE, and only in the middle portion in the NLE; (ii) a higher expression of TH in the neuropil of the VTA in NHE; (iii) a lower C.O. activity in both NLE and NHE; (iv) no differences in the SN. The larger neuron size in both NHE and NLE rats as compared with control rats, along with higher TH expression mainly in the NHE, in absence of any relevant alteration in the SN, reveals an unbalance between the two dopamine systems and a subsequent alteration in limbic (reward, motivation, sustained attention) functions. The decreased C.O. activity might be due to reduced feedback inhibition by striatal GABA neurons and interneurons leading to increased DA neuron firing. In conclusion, the increased behavioral activity and impaired attention observed in the NHE rats are associated to hyperfunctioning MCL system in this genetic model of Attention-Deficit Hyperactivity Disorder (ADHD).

Animals↗

PubMed2002

The Naples High- and Low-Excitability rats: selective breeding, behavioral profile, morphometry, and molecular biology of the mesocortical dopamine system.

The Naples High- (NHE) and Low-Excitability (NLE) rat lines have been selected since 1976 on the basis of behavioral arousal to novelty (Làt-maze). Selective breeding has been conducted under continuous genetic pressure, with no brother-sister mating. The behavioral analyses presented here deal with (1) activity in environments of different complexity, i.e., holeboard and Làt maze; (2) maze learning in hexagonal tunnel, Olton, and Morris water mazes and; (3) two-way active avoidance and conditioned taste aversion tests. Morphometric analyses deal with central dopaminergic systems at their origin and target sites, as well as the density of dopamine transporter immunoreactivity. Molecular biology analyses are also presented, dealing with recent experiments on the prefrontal cortex (PFc), cloning and identifying differentially expressed genes using subtractive libraries and RNAase protection. The divergence between NLE and NHE rats varies as a function of the complexity level of the environment, with an impaired working and reference memory in both lines compared to random bred (NRB) controls. Moreover, data from the PFc of NHE rats show a hyperdopaminergic innervation, with overexpression of mRNA species involved in basal metabolism, and down-regulation of dopamine D1 receptors. Altogether, the evidence gathered so far supports a hyperfunctioning mesocorticolimbic system that makes NHE rats a useful tool for the study of hyperactivity and attention deficit, learning and memory disabilities, and drug abuse.

Analysis of Variance↗