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Fear is an emotional reaction that arises in dangerous situations, inducing the adaptation to an existing condition. This behavior was conserved in all vertebrates throughout evolution and is observed in mammals, birds, fish, amphibians, and reptiles. The neurocircuitry of fear involves areas of the limbic system, cortical regions, midbrain, and brainstem. These areas communicate with each other so that there is an expression of fear and memory formation to deal with the same situation at another time. The effect of nitric oxide (NO) on fear modulation has been explored. NO is a gaseous compound that easily diffuses through the cell membrane and is produced through the oxidation reaction of l-Arginine to l-citrulline catalyzed by nitric oxide synthase (NOS). Activating the intracellular NO receptor (soluble guanylyl cyclase enzyme - sGC) triggers an enzymatic cascade that can culminate in plastic events in the neuron. NOS inhibitors induce anxiolytic-like responses in fear modulation, whereas NO donors promote fear- and anxiety-like behaviors. This review describes the neurobiology of fear in mammals and non-mammals, how NO is produced in the central nervous system, and how NO acts in fear-like behavior.

Nociception alterations are frequent non-motor symptoms of the prodromal phase of Parkinson's disease (PD). The period for the onset of symptoms and the pathophysiological mechanisms underlying these alterations remain unclear. We investigated the course of nociception alterations in a progressive model of parkinsonism induced by reserpine (RES) in rats. Male Wistar rats (6-7 months) received 5 or 10 subcutaneous injections of RES (0.1 mg/kg) or vehicle daily for 20 days. Motor evaluation and nociceptive assessment were performed throughout the treatment. At the end of the treatment rats were euthanized, the brains removed and processed for immunohistochemical analysis (TH and c-Fos). The RES-treated rats exhibited an increased nociceptive response to mechanical and chemical stimulation in the electronic von Frey and formalin tests, respectively. Moreover, these alterations preceded the motor impairment observed in the catalepsy test. In addition, the RES treatment reduced the TH-immunoreactivity in the ventral tegmental area (VTA) and increased the c-Fos expression in the ventral-lateral periaqueductal gray (vlPAG), rostral ventral medulla (RVM) and dorsal raphe nucleus (DRN) after noxious stimuli induced by formalin. Taken together, our results reinforce that nociceptive changes are one of the early signs of PD and monoamine depletion in basal ganglia can be involved in the abnormal processing of nociceptive information in PD.

Geraniol is a monoterpene alcohol that is derived from the essential oils of aromatic plants, with anti-inflammatory, antimicrobial, antioxidant and neuroprotective properties. This study characterized the effect of geraniol on behavior and brainwave patterns in rats. Male rats were submitted to administration of geraniol (25, 50 and 100 mg/kg). The hole board (HB) and open field (OF) tests were performed to evaluate anxiety and motor behavior, respectively. In addition, barbiturate-induced sleeping time (BIST) was used to analyze sedative effect. Finally, electrocorticogram (ECoG) recordings were used to characterize brain-wave patterns. The results showed that geraniol treatment in rats decreased the distance traveled, rearing numbers and lead to increase in immobility time in HB and OF tests. In BIST test, geraniol treatment increased sleep duration but not sleep latency in the animals. Furthermore, geraniol-treated animals demonstrated an increase in the percentage of delta waves in the total spectrum power. Taken together, our results suggested that geraniol exerted a depressant effect on the central nervous system of rats. Keywords: Sedation, Monoterpene, Brain waves, Hypnose, Natural product

Deltamethrin (DM) is widely used in agriculture, veterinary medicine and control of domestic pests. Epidemiological studies suggest that DM exposure is a risk factor for neurodegenerative disorders such as Parkinson’s (PD) and Alzheimer diseases; however the mechanisms are elusive. In the present study we evaluated the effects of intracerebroventricular (i.c.v.) administration of DM on locomotion activity, spatial working memory and dopaminergic pathway in the rat. Middle-aged male Wistar rats received three i.c.v. injections of DM 0.5 μg, DM 5 μg or vehicle, every other day. Across the treatment, the animals were submitted to behavioral evaluation in the catalepsy test, open field test, and spontaneous alternation task. Following completion of behavioral tests, rats were perfused and their brains were processed to tyrosine hydroxylase (TH) immunohistochemistry. We observed that i.c.v. administration of DM 5 μg increased locomotion activity (open field) and caused spatial working memory impairment (spontaneous alternation task). These alterations were accompanied by reduction TH immunoreactivity in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA) and dorsal striatum. Conversely, no motor change was observed in the catalepsy test. These results indicate that i.c.v. administration of DM can cause hyperactivity and cognitive alteration which may be related to disruption of the dopaminergic pathway.

The lizard cortex has remarkable similarities with the mammalian hippocampus. Both regions process memories, have similar cytoarchitectural properties, and are important neurogenic foci in adults. Lizards show striking levels of widespread neurogenesis in adulthood and can regenerate entire cortical areas after injury. Nitric oxide (NO) is an important regulatory factor of mammalian neurogenesis and hippocampal function. However, little is known about its role in nonmammalian neurogenesis. Here, we analyzed the distribution, morphology, and dendritic complexity (Neurolucida reconstructions) of NO-producing neurons through NADPH diaphorase (NADPHd) activity, and how they compare with the distribution of doublecortin-positive (DCX+) neurons in the hippocampal formation of the neotropical lizard Tropidurus hispidus. NADPHd-positive (NADPHd+) neurons in the dorsomedial cortex (DMC; putatively homologous to mammalian CA3) were more numerous and complex than the ones in the medial cortex (MC; putatively homologous to the dentate gyrus). We found that NADPHd+ DMC neurons send long projections into the MC. Interestingly, in the MC, NADPHd+ neurons existed in 2 patterns: small somata with low intensity of staining in the outer layer and large somata with high intensity of staining in the deep layer, a pattern similar to the mammalian cortex. Additionally, NADPHd+ neurons were absent in the granular cell layer of the MC. In contrast, DCX+ neurons were scarce in the DMC but highly numerous in the MC, particularly in the granular cell layer. We hypothesize that NO-producing neurons in the DMC provide important input to proliferating/migrating neurons in the highly neurogenic MC.

Environmental enrichment (EE) has been used to investigate behavioral changes and neuroplasticity in brain in normal and pathological conditions. Besides, the EE has been used to understand the neurobehavioral systems involved in learning experiences, visual inputs, defensive responses, social interactions and memory. However, the required exposure duration to remove aversive memories remains lacking. Therefore, the purpose of the present study was to investigate the time-course effect of EE exposure on the extinction of aversive memory. Young adult male Wistar rats were exposed to two different EE protocols: short-term environmental enrichment (EE2 - animal kept under enriched conditions for two weeks) and long-term environmental enrichment (EE4 - animal kept under enriched conditions for four weeks). The contextual fear conditioning test was used to assess aversive memory. The both EE protocols provide changes in Zif-268 immunoreactivity in mesocorticolimbic areas such as CA1 and central amygdala; however, only short-term EE reduces the ZIF-268 immunoreactivity in VTA. Besides, both EE protocols also provide an increase in TH immunoreactivity in VTA and nucleus accumbens, but only the short-term EE modifies the TH immunoreactivity in CA1 and infralimbic region of the prefrontal cortex. The time-course effect of EE interferes differently on the extinction of aversive memory, being two weeks of exposure with EE sufficient to cause improvement in coping during aversive situations, favoring the extinction of conditioned fear memory.

Parkinson's disease (PD) exhibits sexual differences in susceptibility and pathogenesis in humans, with a high incidence in men and a high severity of motor symptoms in male rodents. Furthermore, studies showed that the administration of low dose of reserpine (RES) induces a progressive appearance of motor alterations similar with parkinsonism in male rodents. Here, we investigated sex differences in motor deficits and tyrosine hydroxylase (TH) immunoreactivity induced by a progressive model of parkinsonism. Gonadally intact male and female Wistar rats and ovariectomized female rats received 15 subcutaneous injections (s.c.) every other day of 0.1 mg/kg of RES or vehicle. The repeated administration of low doses of RES (0.1 mg/kg) produces sexually dimorphic impairments on motor performance (catalepsy and open field test). Intact and ovariectomized females were more resistant to the deleterious effect of repeated administration of reserpine in the early, but this resistance in intact female disappears over time. However, intact females showed a reduction of the TH immunoreactivity in substantia nigra pars compacta, but not in ventral tegmental area and dorsal striatum. These results suggest a possible application of this model in the study of sexual dimorphism throughout the progression of PD.

Parkinson's disease (PD) is a neurodegenerative disease related to the dopaminergic system. The etiology is not fully understood, but it is known that PD is a multifactorial disease that involves genetic and environmental factors, including pesticides. One of these, Deltamethrin (DM), has been widely used for vector control in crops, farming, veterinary medicine and domestic pest control. The purpose of the present study was to investigate the effect of DM repeated administration on motor, cognitive and emotional behavior and dopaminergic parameters. Male Wistar rats received 3 intranasal (i.n.) injections of 100 μL (50 μL/nostril) of DM 0.5 μg/μl or Vehicle (saline solution 0.9%), one injection per week. We observed that DM caused memory (novel object recognition task) and emotion (contextual conditioned fear) alterations accompanied by reduction of TH immunoreactivity in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), and increase of TH immunoreactivity in the dorsal striatum. Motor alterations (catalepsy and open field task) were not observed throughout treatment. These findings suggest a possible early disruption of the dopaminergic pathway caused by repeated DM exposure, similar to that observed in early stages of PD.