Distribution of serotonin 5-HT1A-binding sites in the brainstem and the hypothalamus, and their roles in 5-HT-induced sleep and ingestive behaviors in rock pigeons (Columba livia).

Serotonin 1A receptors (5-HT1ARs), which are widely distributed in the mammalian brain, participate in cognitive and emotional functions. In birds, 5-HT1ARs are expressed in prosencephalic areas involved in visual and cognitive functions. Diverse evidence supports 5-HT1AR-mediated 5-HT-induced ingestive and sleep behaviors in birds. Here, we describe the distribution of 5-HT1ARs in the hypothalamus and brainstem of birds, analyze their potential roles in sleep and ingestive behaviors, and attempt to determine the involvement of auto-/hetero-5-HT1ARs in these behaviors. In 6 pigeons, the anatomical distribution of [(3)H]8-OH-DPAT binding in the rostral brainstem and hypothalamus was examined. Ingestive/sleep behaviors were recorded (1h) in 16 pigeons pretreated with MM77 (a heterosynaptic 5-HT1AR antagonist; 23 or 69 nmol) for 20 min, followed by intracerebroventricular ICV injection of 5-HT (N:8; 150 nmol), 8-OH-DPAT (DPAT, a 5-HT1A,7R agonist, 30 nmol N:8) or vehicle. 5-HT- and DPAT-induced sleep and ingestive behaviors, brainstem 5-HT neuronal density and brain 5-HT content were examined in 12 pigeons, pretreated by ICV with the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (N:6/group). The distribution of brainstem and diencephalic c-Fos immunoreactivity after ICV injection of 5-HT, DPAT or vehicle (N:5/group) into birds provided with or denied access to water is also described. 5-HT1ARs are concentrated in the brainstem 5-HTergic areas and throughout the periventricular hypothalamus, preoptic nuclei and circumventricular organs. 5-HT and DPAT produced a complex c-Fos expression pattern in the 5-HT1AR-enriched preoptic hypothalamus and the circumventricular organs, which are related to drinking and sleep regulation, but modestly affected c-Fos expression in 5-HTergic neurons. The 5-HT-induced ingestivebehaviors and the 5-HT- and DPAT-induced sleep behaviors were reduced by MM77 pretreatment. 5,7-DHT increased sleep per se, decreased tryptophan hydroxylase expression in the raphe nuclei and decreased prosencephalic 5-HT release but failed to affect 5-HT- or DPAT-induced drinking or sleep behavior. 5-HT- and DPAT-induced ingestive and sleep behaviors in pigeons appear to be mediated by heterosynaptic and/or non-somatodendritic presynaptic 5-HT1ARs localized to periventricular diencephalic circuits.

Proanthocyanidin-rich fraction from Croton celtidifolius Baill confers neuroprotection in the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rat model of Parkinson's disease.

We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in olfactory, cognitive and motor functions associated with time-dependent disruption of dopaminergic neurotransmission in different brain structures conceivably analogous to those observed during different stages of Parkinson's disease (PD). On the other hand, the proanthocyanidin-rich fraction (PRF) obtained from the bark of Croton celtidifolius Baill (Euphorbiaceae), a tree frequently found in the Atlantic forest in south Brazil, has been described to have several neurobiological activities including antioxidant and anti-inflammatory properties, which may be of interest in the treatment of PD. The present data indicated that the pretreatment with PRF (10 mg/kg, i.p.) during five consecutive days was able to prevent mitochondrial complex-I inhibition in the striatum and olfactory bulb, as well as a decrease of the enzyme tyrosine hydroxylase expression in the olfactory bulb and substantia nigra of rats infused with a single intranasal administration of MPTP (1 mg/nostril). Moreover, pretreatment with PRF was found to attenuate the short-term social memory deficits, depressive-like behavior and reduction of locomotor activity observed at different periods after intranasal MPTP administration in rats. Altogether, the present findings provide strong evidence that PRF from C. celtidifolius may represent a promising therapeutic tool in PD, thus being able to prevent both motor and non-motor early symptoms of PD, together with its neuroprotective potential.

Distribution of tryptophan hydroxylase-immunoreactive neurons in the brainstem and diencephalon of the pigeon (Columba livia).

The distribution of tryptophan hydroxylase (TPH)-containing perikarya and processes in the brainstem and diencephalon of the pigeon (Columba livia) were investigated using single-labeling chromogenic and double-labeling fluorescence immunohistochemical methods for TPH and 5-HT. TPH-immunoreactive (TPH-ir) perikarya were seen extending from the caudal medulla to mid-hypothalamic levels, located in brainstem regions previously described as containing 5-HT-ir somata. Brainstem TPH-ir cell clusters (the midline raphe, and the dorsolateral and ventrolateral serotonergic cell groups) and the circumventricular cerebrospinal fluid-contacting neurons in the taenia choroidea (in the caudal brainstem), recessus infundibuli and paraventricular organ (in the hypothalamus) were shown to co-express 5-HT immunoreactivity. However, heavily labeled TPH-ir cell clusters were observed in the nucleus premamillaris (PMM), in the stratum cellulare internum (SCI), in the nucleus paraventricularis magnocellularis (PVN) and in the medial border of the nucleus dorsomedialis anterior thalami (DMA). Double-labeling experiments indicated that none of these medial hypothalamic TPH-ir cells were immunoreactive to 5-HT. These cells correspond to dopamine- and melatonin-containing neurons previously found in the avian hypothalamus, and appear to be comparable to the mammalian TPH-ir hypothalamic A11-A13 catecholaminergic somata, suggesting that they may be a conserved attribute in the amniote medial hypothalamus.