Dorsal Raphe Nucleus Lesions Research Articles

Female sexual behaviors in male rats with dorsal raphe nucleus lesions: Treatment with p-chlorophenylalanine

The effects of the serotonin-synthesis inhibitor, p-chlorophenylalanine (PCPA) on female sexual behaviors were examined in male rats with or without lesions (DRL) of the dorsal raphe nucleus, which contains a large number of serotonergic cell bodies. Estrogen-primed castrated males without brain surgery (control) showed extremely low levels of lordosis compared with females. On the other hand, DRL males displayed lordosis response more frequently than control males, but the lordosis quotient (LQ) in this group was lower than that in females. As well as DRL males, all PCPA-treated males showed lordosis, the mean LQ being comparable to the DRL group. Thus, the destruction of the dorsal raphe nucleus or the deprivation of serotonin by PCPA treatment facilitates manifestation of lordosis behavior in male rats. However, synergistic effect of DRL and PCPA treatments on female sexual behaviors have not been observed. The mean LQ in PCPA-treated male rats with DRL was almost the same as in DRL males or PCPA-treated males. These results suggest that the possible site of action of PCPA in regulating female sexual behavior in male rats is the serotonergic neurons in the dorsal raphe nucleus. Furthermore, the lordosis-facilitating effect of DRL is due to destruction of the serotonergic cell bodies in the dorsal raphe nucleus.

Regulation of cortical blood flow by the dorsal raphe nucleus: topographic organization of cerebrovascular regulatory regions.

We examined in rat: (1) the time-course and magnitude of change in cortical blood flow (CoBF) following electrical stimulation of the dorsal raphe nucleus (DRN) and (2) whether DRN lesions affect resting CoBF or the cerebrovascular response to CO2. Animals were anesthetized (chloralose), paralyzed, and artificially ventilated. The effect of stimulus frequency (1-200 Hz) and intensity (10-100 microA) on arterial pressure, heart rate, and CoBF was examined; lesions were made electrolytically. CoBF was measured using a laser-Doppler flowmeter with the probe placed extradurally over the parietal sensorimotor cortex. The DRN was computer reconstructed in three dimensions from Nissl stained coronal sections for localization of electrode placements. Brief stimuli (8 s; n = 6) elicited frequency and intensity-dependent increases in arterial pressure, heart rate, and CoBF. Sustained intermittent trains of stimuli of rostral DRN (200 Hz; 1 s on/1 s off; 70 microA) elicited a decrease (85 +/- 12% of baseline; n = 9) in CoBF (p less than 0.05) while stimulation in caudal DRN resulted in increased CBF (126 +/- 13% of baseline; n = 9). Phenylephrine infusion (0.1-1 microgram; i.v.; n = 8) increased arterial pressure and CoBF less than that elicited by brief DRN stimulation (p less than 0.05). DRN lesions did not affect resting CoBF (140 +/- 25 perfusion units (PU) before; 127 +/- 16 PU after DRN lesion; p greater than 0.05, n = 5) or mean arterial pressure (127 +/- 13 before; 120 +/- 11 after); nor did it affect the cerebrovascular response to change in arterial PCO2. Sustained intermittent stimulation of the DRN can evoke either increases or decreases in CoBF depending on the anatomical sublocalization. The DRN does not tonically maintain resting CoBF, nor participate in the cerebrovascular response to change in PCO2.

Lordosis in male rats: The facilitatory effect of mesencephalic dorsal raphe nucleus lesion

The dorsal raphe nucleus was destroyed (DRL) by a radiofrequency lesion generator in castrated male rats, and lordosis behavior was observed. Five weeks after the surgery, all animals were implanted with two Silastic tubes containing estradiol (E2). Behavioral tests were started 2 days after implantation of E2 and carried out every other day for 16 days. Castrated control and sham-operated control males showed low incidence of lordosis and low lordosis quotient (LQ) throughout the tests, whereas all the DRL males displayed lordosis and the mean LQ of the group was significantly higher than that of control groups, but lower than that of an ovariectomized female group. These results suggest that the dorsal raphe nucleus plays an important role in inhibiting lordosis in male rat brain.

Effect of dorsal raphe nucleus lesions on lordosis in male rats

Effect of dorsal raphe nucleus lesions on lordosis in male rats

The inhibition of proestrous LH surge and ovulation in rats bearing lesions of the dorsal raphe nucleus is mediated by the locus coeruleus

Lesions of the dorsal raphe nucleus (DRn) were shown to block the proestrous surge of LH and the shed of ova normally found the following morning. The possibility that this effect could be mediated by the locus coeruleus (LC) was studied in the present work in view of the fact that stimulation of the LC produced similar responses on LH release and that systemic injection of the ß-adrenergic blocking agent, propranolol, partially prevented the effect of DRn lesions. The blocking effect of DRn lesions on proestrous LH surge and ovulation was reproduced by the injection of either methysergide (1 μg on the day of proestrous), a serotonin (5-HT) blocking agent, or p-chlorophenylalanine (0.5 μg on diestrus 1 and diestrus 2), an inhibitor of 5-HT synthesis, into the LC of normal cycling rats. On the contrary, the injection of 5-HT (1 μg on the day of proestrus) into the LC of rats bearing DRn lesions restored the normal LH surge and ovulation. It is concluded that serotonergic afferents into the LC from the DRn tonically inhibit the activity of LC neurons and that the interference of this inflow results in an activation of neurons and thereby in inhibition of LH release.

Increase of self-mutilation behavior in forelimb deaf-ferented rats, following stimulation of the dorsal raphe nucleus

The role of dorsal raphe nucleus (DRN) was studied in rats which develop scratching or/and self-mutilation after deafferentation of brachial plexus. The extent of the lesions was measured in four groups of deafferented rats. Two control groups: implanted and not implanted, a group of animals in which DRN was stimulated, and a group in which it was electrolytically destroyed. We observed an increase of scratching and self-mutilation in the implanted group but overall in the stimulated group, and no change in the abnormal behavior was provoked by DRN lesion.

Role of the hypothalamic paraventricular nucleus in the secretion of thyrotropin under adrenergic and cold-stimulated conditions in the rat.

To investigate the role of central noradrenergic systems in the regulation of TSH secretion, clonidine (an alpha 2-adrenergic agonist) and an electrolytic procedure were used. The administration of a small dose (50 micrograms/kg, iv) of clonidine induced a significant rise in immunoreactive TSH levels in the plasma with a short time lag in unanesthetized, unrestrained rats. The TSH-stimulating effect of clonidine was significantly reduced by passive immunization with rabbit antiserum to TRH. In rats with midbrain transection, the plasma TSH elevation in response to clonidine did not differ from that of sham-operated controls, whereas bilateral lesions in the paraventricular nucleus (PVN) markedly diminished the TSH secretory response. In contrast, the placement of electrolytic lesions in the dorsal raphe nucleus caused a significant increase in the basal TSH concentrations within 3 days, and magnified the TSH response to alpha 2-adrenergic stimulation. Acute exposure to cold (2-3 C) induced a prompt increase in the plasma TSH concentrations in normal rats. Bilateral lesions in the medial preoptic/anterior hypothalamus had no effect on the TSH response to cold exposure. In rats with the dorsal raphe nucleus lesions no significant effect was observed on the responsiveness to cold. In rats bearing PVN lesions, however, plasma TSH levels decreased significantly compared with sham-operated controls within 4 days, and also remained at basal levels during the whole period of cold exposure. The results of the present study provide evidence supporting the hypothesis that the PVN is essential for the process of TRH-TSH secretion, which is accelerated under cold-stimulated conditions, presumably via the central noradrenergic system(s).

Serotonergic innervation of the forebrain: Effect of lesions on serotonin and tryptophan hydroxylase levels

Concentrations of serotonin and tryptophan hydroxylase activity in individual hypothalamic and limbic nuclei, as well as cortical regions, were measured by radioenzymatic microassays after dorsal raphe nucleus lesions and various surgical transections of the brain stem. Fourteen days after lesioning of the dorsal raphe nucleus there were 43-65% decreases in 5-HT concentrations of certain hypothalamic and limbic nuclei. More pronounced decreases were found in the parietal cortex and in the locus coeruleus and substantia nigra. Degenerations of nerve terminals in various regions of the hypothalamus and the limbic system were detected by electron microscopic studies 1-8 days after dorsal raphe nucleus lesions. There was no change in the 5-HT concentration of the spinal cord following dorsal raphe nucleus lesions. Surgical transections at the level of mesencephalic-pontine junction caused no significant changes in 5-HT concentrations or tryptophan hydroxylase levels in the hypothalamus, limbic system, cerebral cortex or spinal cord. Serotonergic fibers ascending from the mesencephalic raphe nuclei constitute a well circumscribed bundle dorsal to the interpeduncular nucleus. The axons enter the hypothalamus between the mammillary body and crus cerebri just ventral to the medial forebrain bundle. The ascending pathway contains all the ascending 5-HT fibers innervating the hypothalamus and the rostral limbic and cortical areas.