A genomic region neighboring the a-synuclein gene, on rat chromosome 4, has been associated with anxiety-and alcohol-related behaviors in different rat strains. In this study, we have investigated potential molecular and physiological links between a-synuclein and the behavioral differences observed between Lewis (LEW) and Spontaneously Hypertensive (SHR) inbred rats, a genetic model of anxiety. As expected, LEW rats appeared more fearful than SHR rats in three anxiety models: open field, elevated plus maze and light/dark box. Moreover, LEW rats displayed a higher preference for alcohol and consumed higher quantities of alcohol than SHR rats. a-Synuclein mRNA and protein concentrations were higher in the hippocampus, but not the hypothalamus of LEW rats. This result inversely correlated with differences in dopamine turnover in the hippocampus of LEW and SHR rats, supporting the hypothesis that a-synuclein is important in the downregulation of dopamine neurotransmission. A novel single nucleotide polymorphism was identified in the 3 0 -untranslated region (3 0 -UTR) of the asynuclein cDNA between these two rat strains. Plasmid constructs based on the LEW 3 0 -UTR sequence displayed increased expression of a reporter gene in transiently transfected PC12 cells, in accordance with in-vivo findings, suggesting that this nucleotide exchange might participate in the differential expression of a-synuclein between LEW and SHR rats. These results are consistent with a novel role for a-synuclein in modulating rat anxiety-like behaviors, possibly through dopaminergic mechanisms. Since the behavioral and genetic differences between these two strains are the product of independent evolutionary histories, the possibility that polymorphisms in the a-synuclein gene may be associated with vulnerability to anxiety-related disorders in humans requires further investigation.

Although purinergic receptor activity has lately been associated with epilepsy, little is known about the exact role of purines in epileptogenesis. We have used a rat model of temporal lobe epilepsy induced by pilocarpine to study the dynamics of purine metabolism in the hippocampus during different times of status epilepticus (SE) and the chronic phase. Concentrations of adenosine 5′-triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine in normal and epileptic rat hippocampus were determined by microdialysis in combination with high-performance liquid chromatography (HPLC). Extracellular ATP concentrations did not vary along 4 h of SE onset. However, AMP concentration was elevated during the second hour, whereas ADP and adenosine concentrations augmented during the third and fourth hour following SE. During chronic phase, extracellular ATP, ADP, AMP, and adenosine concentrations decreased, although these levels again increased significantly during spontaneous seizures. These results suggest that the increased turnover of ATP during the acute period is a compensatory mechanism able to reduce the excitatory role of ATP. Increased adenosine levels following 4 h of SE may contribute to block seizures. On the other hand, the reduction of purine levels in the hippocampus of chronic epileptic rats may result from metabolic changes and be part of the mechanisms involved in the onset of spontaneous seizures. This work provides further insights into purinergic signaling during establishment and chronic phase of epilepsy.

1 The effects of the main component of the Tityus serrulatus scorpion venom, toxin TsTX-I, were studied on the contractility and release of neurotransmitters in the rat vas deferens. Since TsTX-I is known to act on sodium channels, we used veratridine, another sodium channel agent, for comparison. 2 Toxin TsTX-I induced concentration-dependent contractions with an EC 50 value of 47.870.1 nM and a maximum effect of 84.4710.4% of that for BaCl 2 . 3 Contractions by TsTX-I were abolished by denervation or tetrodotoxin (0.1 mM), showing that the toxin effects depend on the integrity of sympathetic nerve terminals. 4 To check for the presence of a noradrenergic component, experiments were conducted after removal of adrenergic stores in nerve terminals by reserpinization (10 mg kg À1 , 24 h prior to experiments) or blockade of a 1 adrenoceptors by prazosin (30 mM), showing that these procedures did not modify the response to TsTX-I, and therefore that adrenoceptors were not involved in contractions. 5 To check for the presence of a purinergic component, experiments were carried out after blockade of P 2X receptors by suramin (0.1 mM) or desensitization by a,b-methylene-ATP (30 mM). These agents greatly abolished the contractile response to TsTX-I (about 83% by desensitization and 96% by suramin), showing the involvement of purinergic receptors. 6 The release of noradrenaline and purinergic agents (ATP, ADP, AMP and adenosine) was detected by HPLC. Together, the total release of purines in the presence of TsTX-I was about 42 times higher than in the control group. In contrast, TsTX-I did not modify the overflow of noradrenaline, showing that the release was selective for purines. 7 The release of purinergic agents was reduced by the N-type calcium channel blocker o-conotoxin GVIA (1 mM) and by the P/Q-type blocker o-conotoxin MVIIC (1 mM), showing that the effects of TsTX-I are calcium-dependent. 8 The results show that TsTX-I produced a selective release of purines from postganglionic sympathetic nerves in the rat vas deferens.

In adult female mammals, reproductive experience (e.g., mating, pregnancy, parturition, and lactation) has long-term behavioral, endocrine, and neurochemical implications. This experience causes behavioral and neurochemical changes that involve several brain areas important for the expression of maternal behavior. The present study showed that lactating rats exhibited reduced general locomotor activity in the open field test compared with virgin animals. Our hypothesis was that nucleus accumbens dopamine, which regulates maternal behavior in lactating rats, is also involved in the low expression of maternal locomotion in the open field test observed during the early stages of lactation and reflects decreased motivation.Initially we compared open field behavior in virgin and lactating rats to confirm our previous data. Thus, the in vivo release of dopamine in the nucleus accumbens in virgin and lactating female rats was measured. Perfusate concentrations of extracellular dopamine and its metabolites showed no differences between virgin and lactating rats. Thus, the reduced general activity observed in lactating rats might not be related to intra-nucleus accumbens dopamine control.

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