5-HT1A autoreceptor modulation of locomotor activity induced by nitric oxide in the rat dorsal raphe nucleus

The dorsal raphe nucleus (DRN) is the origin of ascending serotonergic projections and is considered to be an important component of the brain circuit that mediates anxiety- and depression-related behaviors. A large fraction of DRN serotonin-positive neurons contain nitric oxide (NO). Disruption of NO-mediated neurotransmission in the DRN by NO synthase inhibitors produces anxiolytic- and antidepressant-like effects in rats and also induces nonspecific interference with locomotor activity. We investigated the involvement of the 5-HT1A autoreceptor in the locomotor effects induced by NO in the DRN of male Wistar rats (280-310 g, N = 9-10 per group). The NO donor 3-morpholinosylnomine hydrochloride (SIN-1, 150, and 300 nmol) and the NO scavenger S-3-carboxy-4-hydroxyphenylglycine (carboxy-PTIO, 0.1-3.0 nmol) were injected into the DRN of rats immediately before they were exposed to the open field for 10 min. To evaluate the involvement of the 5-HT1A receptor and the N-methyl-D-aspartate (NMDA) glutamate receptor in the locomotor effects of NO, animals were pretreated with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 8 nmol), the 5-HT1A receptor antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY-100635, 0.37 nmol), and the NMDA receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (AP7, 1 nmol), followed by microinjection of SIN-1 into the DRN. SIN-1 increased the distance traveled (mean ± SEM) in the open-field test (4431 ± 306.1 cm; F7,63 = 2.44, P = 0.028) and this effect was blocked by previous 8-OH-DPAT (2885 ± 490.4 cm) or AP7 (3335 ± 283.5 cm) administration (P < 0.05, Duncan test). These results indicate that 5-HT1A receptor activation and/or facilitation of glutamate neurotransmission can modulate the locomotor effects induced by NO in the DRN.

[ effect of hydrochloric extraction of valerian on number and size of raphe magnus neurons in adult rats]

Effective materials from Valerian officinalis L. have too much usage in the pharmacological industry. It is used as a sedative, anticonvulsion, and antidepressant drug. Serotonin has a widespread role in vital function such as sleep, awareness and calmness. In this study we evaluated the effect of hydrochloric extract of valerian on number and size of raphe magnus neurons in adult rat. In this experimental study, which was conducted at Yasuj University of Medical Sciences in 2009, forty adult Wistar rats, each 170-250 gr, were divided randomly into four groups [one control group and three experimental groups]. The animals were injected daily for one month with doses of 300, 400 and 600 mg/kg of the extract. The control group just received distilled water. After transcardial perfusion, the whole brain was separated, then 10 micro m sections of the brain stem were prepared, and hematoxylin and eosin [H and E] staining were done. Number and size of raphe magna neurons were observed under light microscope. The gathered data were analyzed by the SPSS software using One-way ANOVA and LSD. The control group did not statistically show significant changes in number of raphe magna neurons. Comparison of the means of long and short diameter neurons showed significant increases in experimental groups with control group [P<0.05]. In experimental groups the neuron nucleuses were more euchromatic than the control group. Hydrochloric extract of valerian has no effect on raphe magnus neurons, but it is effective on neurons' size. It can be concluded that the extract increases both neurons activity and serotonin secretion

Chronic excitotoxic lesion of the dorsal raphe nucleus induces sodium appetite

We determined if the dorsal raphe nucleus (DRN) exerts tonic control of basal and stimulated sodium and water intake. Male Wistar rats weighing 300-350 g were microinjected with phosphate buffer (PB-DRN, N = 11) or 1 æg/0.2 æl, in a single dose, ibotenic acid (IBO-DRN, N = 9 to 10) through a guide cannula into the DRN and were observed for 21 days in order to measure basal sodium appetite and water intake and in the following situations: furosemide-induced sodium depletion (20 mg/kg, sc, 24 h before the experiment) and a low dose of dietary captopril (1 mg/g chow). From the 6th day after ibotenic acid injection IBO-DRN rats showed an increase in sodium appetite (12.0 ± 2.3 to 22.3 ± 4.6 ml 0.3 M NaCl intake) whereas PB-DRN did not exceed 2 ml (P < 0.001). Water intake was comparable in both groups. In addition to a higher dipsogenic response, sodium-depleted IBO-DRN animals displayed an increase of 0.3 M NaCl intake compared to PB-DRN (37.4 ± 3.8 vs 21.6 ± 3.9 ml 300 min after fluid offer, P < 0.001). Captopril added to chow caused an increase of 0.3 M NaCl intake during the first 2 days (IBO-DRN, 33.8 ± 4.3 and 32.5 ± 3.4 ml on day 1 and day 2, respectively, vs 20.2 ± 2.8 ml on day 0, P < 0.001). These data support the view that DRN, probably via ascending serotonergic system, tonically modulates sodium appetite under basal and sodium depletion conditions and/or after an increase in peripheral or brain angiotensin II.

A comparison of the effects of eserine sulfate on the activity of medullary raphe neurons in the anesthetized rabbit and rat

1. Medullary raphe neurons are involved in the control of sympathetic activity during desynchronized sleep (DS). Eserine sulfate induces a state with the somatic and visceral signs of DS in decerebrate animals. The rabbit and rat display diverse hemodynamic patterns during DS. 2. To determine whether eserine sulfate provokes different responses in the medullary raphe neuron population of these different species, the drug (100 mg/kg, i.v.) was administered to urethane-anesthetized (1.2 g/kg, i.v.) rabbits (1.5-3.0 kg) and rats (Wistar, 260-310 g). 3. Extracellular activity was recorded from 66 neurons in 30 rats. Cholinergic stimulation provoked an increase in discharge rate (DR) in 45 neurons (68), a decrease in 8 neurons (12) and no change in 13 neurons (20). Recordings were obtained from 30 neurons in 11 rabbits. Stimulation of these cells provoked an increase in DR in 17 neurons (57), a decrease in DR in 7 neurons (23) and no change in 6 neurons (20). Interspike interval and auto-correlation analysis was performed on 28 rat and rabbit neurons. No significant difference was found between the rat and the rabbit with respect to the number of the neurons which were either inhibited or excited by cholinergic stimulation (P > 0.05). Similarly, unit response to eserine was not related to whether the unit displayed regular or irregular DR. 4. Therefore, we suggest that the diverse hemodynamic patterns during DS and the distinct cardiovascular responses to raphe nuclei stimulation are not due to differences in the organization of the raphe nuclei themselves but to differences in their axonal projections or in the postsynaptic receptors activated in the intermediolateral cell column or other postsynaptic targets.

Dorsal raphe nucleus lesions have no effect on neuroleptic-induced catalepsy and on the anticataleptic activity of buspirone

The anxiolytic drug buspirone (BUS) and other central 5-HT-1A receptor ligands are capable of reducing neuroleptic-induced catalepsy in rodents. The dorsal raphe nucleus (DRN) is reported to be an important source of serotonergic projections to the basal ganglia, the site of neuroleptic action. The present study was designed to evaluate the participation of the DRN in the anticataleptic effect of BUS on male Wistar rats. Rats were submitted to electrolytic or sham DRN lesion under barbiturate anesthesia. Ten days later, the animals were injected with BUS (5 mg/kg,ip) or saline ( 1 ml, ip) and catalepsy was induced 20 min later with haloperidol (1 mg/kg, ip). Saline-injected DRN-lesioned and sham-lesioned rats displayed similar catalepsy score and BUS significantly and similarly reduced the catalepsy scores in both groups. The results suggest that, in producing anticataleptic effects, BUS interacts at sites other than the DRN. The participation of other raphe nuclei in the anticataleptic effect of BUS is currently under investigation