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1 Using brain microdialysis, we compared the relative role of 5-hydroxytryptamine (5-HT; serotonin) blockade and somatodendritic 5-HT 1A and/or terminal 5-HT 1B autoreceptor activation in the control of 5-HT output. 2 Fluoxetine (10 mg kg 71 i.p.) doubled the 5-HT output in frontal cortex and dorsal hippocampus. The 5-HT 1A receptor antagonist WAY 100635, (0.3 mg kg 71 s.c.) potentiated the eect of¯uoxetine only in frontal cortex (to *500 % of baseline). 3 Methiothepin (10 mg kg 71 s.c.) further enhanced the 5-HT rise induced by¯uoxetine+WAY 100635, to 835+179% in frontal cortex and 456+24% in dorsal hippocampus. Locally applied, methiothepin potentiated the¯uoxetine-induced 5-HT rise more in the former area. 4 The selective 5-HT 1B receptor antagonist SB-224289 (4 mg kg 71 i.p.) enhanced the eect of uoxetine (10 mg kg 71 i.p.) in both areas. As with methiothepin, SB-224289 (4 mg kg 71 i.p.) further enhanced the 5-HT increase produced by¯uoxetine+WAY 100635 more in frontal cortex (613+134%) than in dorsal hippocampus (353+59%). 5 Locally applied,¯uoxetine (10 ± 300 mM; EC 50 =28 ± 29 mM) and citalopram (1 ± 30 mM; EC 50 =1.0 ± 1.4 mM) increased the 5-HT output two to three times more in frontal cortex than in dorsal hippocampus. 6 These data suggest that the comparable 5-HT increase produced by systemic¯uoxetine in frontal cortex and dorsal hippocampus results from a greater eect of reuptake blockade in frontal cortex that is oset by a greater autoreceptor-mediated inhibition of 5-HT release. As a result, 5-HT autoreceptor antagonists preferentially potentiate the eect of¯uoxetine in frontal cortex.

In rodents, repeated exposure to unavoidable aggression followed by sustained sensory treat can lead to prolonged social aversion. The chronic social defeat stress model explores that phenomenon and it has been used as an animal model for human depression. However, some authors have questioned whether confounding effects may arise as the model also boosts anxiety-related behaviors. Despite its wide acceptance, most studies extract limited information from the behavior of the defeated animal. Often, the normalized occupancy around the social stimulus, the interaction zone, is taken as an index of depression. We hypothesized that this parameter is insufficient to fully characterize the behavioral consequences of this form of stress. Using an ethological approach, we showed that repeated social defeat delayed the expression of social investigation in long (10 min) sessions of social interaction. Also, the incidence of defensive behaviors, including stretched-attend posture and high speed retreats, was significantly higher in defeated mice in comparison to controls. Interestingly, a subpopulation of defeated mice showed recurrent and non-habituating stretched-attend posture and persistent flights during the entire session. Two indexes were created based on defensive behaviors to show that only recurrent flights correlates with sucrose intake. Together, the present study corroborates the idea that this model of social stress can precipitate a myriad of behaviors not readily disentangled. We propose that long sessions (>150 s) and detailed ethological evaluation during social interaction tests are necessary to provide enough information to correctly classify defeated animals in terms of resilience and susceptibility to social defeat stress.

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The effects of chronic administration of alpha-tocopherol or melatonin, or acute ascorbic acid administration on the convulsant action of methylmalonic acid (MMA) were investigated in adult male rats. Animals were chronically injected with alpha-tocopherol (40 mg kg(-1), i.p.), melatonin (5 mg kg(-1), i.p.) or vehicle for 7 days. Buffered MMA (6 micromol/2 microl) or NaCl (9 micromol/2 microl) was injected intrastriatally and the animals were observed for the appearance of clonic or tonic-clonic convulsions and rotational behavior. Ascorbic acid (100 mg kg(-1), s.c.) was administered 30 min before MMA injection. Alpha-tocopherol and ascorbic acid pretreatment decreased the duration of the convulsive episodes and the rotational behavior elicited by MMA. This study provides evidence that free radical generation may participate in the convulsant effects of methylmalonic acid.

Queiroz CM, Gorter JA, Lopes da Silva FH, Wadman WJ. Dynamics of evoked local field potentials in the hippocampus of epileptic rats with spontaneous seizures. J Neurophysiol 101: 1588 -1597, 2009. First published October 8, 2008 doi:10.1152/jn.90770.2008. A change in neuronal network excitability within the hippocampus is one of the hallmarks of temporal lobe epilepsy (TLE). In the dentate gyrus (DG), however, neuronal loss and mossy fiber sprouting are associated with enhanced inhibition rather than progressive hyperexcitability. The aim of this study was to investigate how alterations in excitability take place in association with spontaneous seizures expressed in the DG before, during, and after a seizure. For this purpose, we used freely moving rats that had developed spontaneous seizures after a kainateinduced status epilepticus (SE). Continuous EEG was recorded in the DG during several days along with local field potentials (LFPs) that were evoked every 15-30 s by applying paired-pulse stimuli to the angular bundle. Input-output relations showed increased paired pulse depression in epileptic compared with control rats, suggesting a rather strong inhibition in the DG during the interictal state. A characteristic pattern of changes in intrinsic excitability was observed during the ictal period: an increase in the population spike (PS) amplitude, mostly during the early phase of a seizure and often followed by a decrease of the main evoked potential amplitude. The paired-pulse extracellular postsynaptic potential (fEPSP) ratio increased during the seizure and did slowly recover to preictal levels after the seizure ended. Although clear changes in excitability occurred during and after seizure activity, changes of LFP parameters were more subtle before seizure onset; a significant reduction of LFP and PS amplitudes was observed that started 1-2 min in advance in ϳ33% of the cases; in ϳ18%, an increase of LFP/PS amplitude was observed; in the other cases, no significant change was observed. Taken together, these results provide evidence that, in this experimental model, DG physiology is more likely to follow the already ongoing seizure activity rather than to contribute to its generation.Epilepsy is a syndrome characterized by recurrent and spontaneous seizures produced by abnormal paroxysmal activities of neuronal ensembles. It is commonly assumed that spontaneous seizures appear when enhanced neuronal excitability reaches a threshold combined with a high level of synchrony between neurons (Prince et al. 1983;Traub and Wong 1982). It is important to understand the changes in the excitability of neuronal networks in relation to the occurrence of seizures to obtain insight into the mechanism that determines their occurrence. This is particularly important in the case of temporal lobe epilepsy (TLE), where a number of changes at the cellular level are now known, although the contributions of different subsystems within the hippocampal formation are not yet precisely understood.An appropriate experimental model of...

Absolute pitch (AP) is the ability to identify and name the pitch of a sound without external reference. Often, accuracy and speed at naming isolated musical pitches are correlated with demographic, biological, and acoustical parameters to gain insight into the genesis and evolution of this ability in specific cohorts. However, the majority of those studies were conducted in North America, Europe, or Asia. To fill this gap, here we investigated the pitch-naming performance in a large population of Brazilian conservatory musicians (N = 200). As previously shown, we found that the population performance was rather a continuum than an “all-or-none” ability. By comparing the observed distribution of correct responses to a theoretical binomial distribution, we estimated the prevalence of AP as being 18% amongst regular music students. High accuracy thresholds (e.g., 85% of correct responses) yielded a prevalence of 4%, suggesting that AP might have been underestimated in previous reports. Irrespective of the threshold used, AP prevalence was higher in musicians who started their musical practice and formal musical education early in life. Finally, we compared the performance of those music students (average proficiency group) with another group of students selected to take part in the conservatory orchestra (high proficiency group, N = 30). Interestingly, the prevalence of AP was higher in the latter in comparison to the former group. In addition, even when the response was incorrect, the mean absolute deviation from the correct response was smaller in the high proficiency group compared to the average proficiency group (Glass's Δ: 0.5). Taken together, our results show that the prevalence of AP in Brazilian students is similar to other non-tonal language populations, although this measure is highly dependent on the scoring threshold used. Despite corroborating that early involvement with musical practice and formal education can foster AP ability, the present data suggest that music proficiency may also play an important role in AP expression.