Near the end of the second postnatal week motor activity is increased soon after ethanol administration (2.5 g/kg) while sedation-like effects prevail when blood ethanol levels reach peak values. This time course coincides with biphasic reinforcement (appetitive and aversive) effects of ethanol determined at the same age. The present experiments tested the hypothesis that ethanol-induced activity during early development in the rat depends on the dopamine system, which is functional in modulating motor activity early in ontogeny. Experiments 1a and 1b tested ethanol-induced activity (0 or 2.5 g/kg) after a D1-like (SCH23390; 0, 0.015, 0.030 or 0.060 mg/kg) or a D2-like (sulpiride; 0, 5, 10 or 20 mg/kg) receptor antagonist, respectively. Ethanol-induced stimulation was suppressed by SCH23390 or sulpiride. The dopaminergic antagonists had no effect on blood ethanol concentration (Experiments 2a and 2b). In Experiment 3, 2.5 g/kg ethanol increased dopamine concentration in striatal tissue as well as locomotor activity in infant Wistar rats. Adding to our previous results showing a reduction in ethanol induced activity by a GABA B agonist or a nonspecific opioid antagonist, the present experiments implicate both D1-like and D2-like dopamine receptors in ethanol-induced locomotor stimulation during early development. According to these results, the same mechanims that modulate ethanol-mediated locomotor stimulation in adult rodents seem to regulate this particular ethanol effect in the infant rat.

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase identified by its close sequence homology to the classic members of the cdk family of regulating cell cycle progression proteins. Cdk5 is a unique member of this family that is active in post-mitotic neurons. Like other Cdks, however, monomeric Cdk5 shows no enzymatic activity and requires association with a regulatory subunit, either p35 or p39, which are brain-specific (Ishiguro et al. 1994;Lew et al. 1994;Tsai et al. 1994;Tang et al. 1995). Moreover, in vivo evidence has demonstrated that the level of p35 regulating protein is a rate-limiting factor for the up-regulation of Cdk5 activity (Takahashi et al. 2005). Several lines of evidence suggest that the Cdk5/p35 complex plays a critical role in normal brain development, regulating neuronal migration and differentiation, axodendritic organization and laminar architecture, trafficking and transport (Nikolic et al. 1996;Ohshima et al. 1996;Chae et al. 1997;Paglini et al. 1998;Ratner et al. 1998;Kwon and Tsai 1998;Ohshima et al. 1999;Kwon et al. 1999;Smith and Tsai 2002;Dhariwala and Rajadhyaksha 2008). Besides its essential role in brain development, Cdk5 has also been implicated in dopaminergic transmission in the post-natal brain, where it modulates Received January 18, 2010; revised manuscript received April 6, 2010; accepted April 7, 2010. Address correspondence and reprint requests to Gabriela Paglini, PhD, Laboratory of Neurobiology and Cell Biology, Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET), Av. Friuli 2434, 5016 Có rdoba Argentina. E-mail: gpaglini@immf.uncor.eduAbbreviations used: ADHD, attention deficit hyperactivity disorder; Amph, D-anphetamine sulfate; Cdk5, cyclin-dependent kinase 5; CPu, striatum-caudate putamen; DA, dopamine; DARPP-32, dopamine and cAMP regulated phosphoprotein, molecular mass 32 kDa; DOPAC, 3,4-dihydroxyphenylacetic acid; EPM, elevated plus maze; Mtph, methylphenidate; NAc, nucleus accumbens; NHS, normal horse serum; PBS, phosphate-buffered saline; PKA, cAMP-dependent kinase; TBST, trisbuffered saline-tween 20; TH, tyrosine hydroxylase; WT, wild type. AbstractCyclin-dependent kinase 5/p35 kinase complex plays a critical role in dopaminergic neurotransmission. Dysregulation of dopamine (DA) signaling is associated with neurological and neuropsychiatric disorders. As cyclin-dependent kinase 5 (Cdk5) requires association with p35 for its proper activation, we hypothesized that dysregulation of Cdk5 activity might have an effect on striatal-mediated behavior. We used a mutant mouse, deficient in p35 protein (p35 KO), which displayed reduced Cdk5 activity. Throughout behavioral and biochemical characterization of naïve and psychostimulanttreated mice, we demonstrated that only juvenile p35 KO mice displayed spontaneous hyperactivity, responded with a paradoxical hypolocomotor effect to psychostimulant drugs and exhibited deficit on proper behavioral inhibition. Strong immunolabeling for tyrosine-hydroxylase and high ...

Lead (Pb) is a developmental neurotoxicant found in industrial activities, many of them already prohibited worldwide. This study aimed to evaluate current blood Pb (PbB) levels in children in Cordoba, Argentina, and to compare these with similar studies performed before Pb was banned in gasoline in 1996. We also sought to identify mechanistically relevant biomarkers by measuring δ-aminolevulinic acid dehydratase (δ-ALAD), superoxide dismutase (SOD), and catalase (CAT) activities. We finally aimed to determine whether sociodemographic characteristics are associated with Pb toxicity. Blood samples collected from 161 healthy children between September 2009 and February 2010 revealed mean PbB levels of 2.58 ± 0.30 µg/dl. Enzymatic δ-ALAD, CAT, and SOD activities showed no significant variations when plotted against PbB levels. Finally, children living in the suburbs have higher PbB levels than their city counterparts, while low socioeconomic status increased δ-ALAD inhibition compared with that of middle-income children. Overall, these results evidenced a substantial reduction in exposure to Pb in this pediatric population over a decade after Pb was restricted in gasoline and reveal the importance of pursuing novel biomarkers of toxicity along with the sociodemographic profile to complement Pb diagnosis.

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Adolescents are sensitive to the anxiolytic effect of ethanol, and evidence suggests that they may be more sensitive to stress than adults. Relatively little is known, however, about age-related differences in stress modulation of ethanol drinking or stress modulation of ethanol-induced sedation and hypnosis. We observed that chronic restraint stress transiently exacerbated free-choice ethanol drinking in adolescent, but not in adult, rats. Restraint stress altered exploration patterns of a light-dark box apparatus in adolescents and adults. Stressed animals spent significantly more time in the white area of the maze and made significantly more transfers between compartments than their non-stressed peers. Behavioral response to acute stress, on the other hand, was modulated by prior restraint stress only in adults. Adolescents, unlike adults, exhibited ethanol-induced motor stimulation in an open field. Stress increased the duration of loss of the righting reflex after a high ethanol dose, yet this effect was similar at both ages. Ethanol-induced sleep time was much higher in adult than in adolescent rats, yet stress diminished ethanol-induced sleep time only in adults. The study indicates age-related differences that may increase the risk for initiation and escalation in alcohol drinking.

The effect of transport stress on blood corticosterone levels in captive Greater Rheas was investigated. Twelve adult individuals (7 males; 5 females) were loaded in pairs inside wooden crates and transported along a paved road for 30 min. Blood samples were taken before the individuals were introduced into the crate (baseline value) and immediately after they were unloaded (30 min after capture). To assess whether corticosterone levels were affected by the blood sampling procedure per se, another 6 (nontransport) control birds (3 males; 3 females) were also captured and sampled at the same times as their transported counterparts. Plasma corticosterone concentrations were measured using a commercially available corticosterone (125)I radio-immunoassay kit. Baseline corticosterone levels were similar in the control and transported birds (9.0 ± 1.6 and 10.4 ± 0.8 ng/mL, respectively). Transportation induced a highly significant (P < 0.001), more than 40-fold increase in the corticosterone levels (433.6 ± 35.4 ng/mL) that was about 5 times higher (P < 0.001) than in their nontransported counterparts (88.4 ± 14.8 ng/mL). The present findings suggest that Greater Rhea is a species highly sensitive to stressful manipulations. Both blood sampling and transportation induced highly significant adrenocortical responses. Considering that transportation is one of the unavoidable common practices in the management of Greater Rheas and, as shown in the present study, that it induces a significant 40-fold corticosterone stress response, efforts should focus on helping to generate management transport standards for optimization of the welfare of this ratite.

The Greater Rhea (Rhea americana) is a nearthreatened species. Wild populations are affected by human activities, such as illegal hunting, egg harvesting and conversion of natural habitats to croplands. An indicator of disturbances is the increase of the glucocorticoid corticosterone, a stress hormone that helps to cope with lifethreatening situations. Here, we evaluate and characterize adrenocortical function in the Greater Rhea by validating the use of a radioimmunoassay (RIA) to assess fecal glucocorticoid metabolite concentrations, and by comparing the time course of plasma corticosterone and fecal immunoreactive glucocorticoid metabolite excretion. An adrenocorticotropic hormone (ACTH) challenge was performed and serial blood and fecal (cecal and rectal) samples were collected and analyzed by a corticosterone RIA.High-performance liquid chromatography (HPLC) was employed to characterize fecal immunoreactive glucocorticoid metabolites. HPLC analysis revealed the presence of two immunoreactive glucocorticoid metabolites in rectal and cecal Rhea feces. Greater Rheas responded to the ACTH challenge with a 30-fold increase in plasma corticosterone concentration 2 h post-injection, and a 30-to 40-fold increase in concentrations of glucocorticoid metabolites from rectal feces 4-6 h post-injection. In cecal feces, ACTH challenge produced an 11-fold increase. Therefore, collection of rectal feces would be more appropriated to ensure detection of minor increases in adrenocortical activity in this species. The adrenocortical response to ACTH found in Rhea was higher than what is usually observed in other birds and might be associated with their flightless condition and the use of running as an antipredator strategy.