Effects Of Raphe Lesions Research Articles

Effect of raphe lesions on the development of acute tolerance to ethanol and pentobarbital.

The effect of electrolytic lesions in the median and dorsal raphe nuclei was tested on acute tolerance development to ethanol and pentobarbital in the rat, as measured by motor impairment on the moving belt test. Acute tolerance to ethanol (1.7 g/kg, IP) or pentobarbital (17.5 mg/kg, IP) was monitored at 12.5, 25, or 50 min in separate subgroups tested only once each. One week of recovery was allowed between ethanol and pentobarbital tests. Median raphe lesions delayed the development of acute tolerance, whereas dorsal raphe lesions produced a negligible effect. These results were seen with both ethanol and pentobarbital. The mesolimbic 5-HT pathway from the median raphe nucleus is important in the development of acute tolerance to ethanol and pentobarbital, as was shown to be the case previously for chronic tolerance.

Effect of raphe lesions on the development of chronic tolerance to pentobarbital and cross-tolerance to ethanol.

Sham and electrolytic lesions of the dorsal, median, and median + dorsal raphe nuclei were made in different groups of rats, and the differential patterns of regional 5-HT depletion were verified chemically. One week later, an initial dose-response curve for the motor impairment effect (moving belt test) of pentobarbital was obtained. Matched subgroups of the animals in each lesioned group received daily gavage with either pentobarbital (50 mg/kg) or water for 36 days. Tolerance to the motor impairment effect of pentobarbital was measured at 4-day intervals. Lesions of the dorsal raphe nucleus had no influence on the development of tolerance, whereas median and median + dorsal raphe lesions resulted in slower development of tolerance, though plasma pentobarbital levels were unaltered. The effect of the combined lesion was similar to that of the median raphe lesion alone. A separate study revealed a similar differential effect of median versus dorsal raphe lesions on the development of cross-tolerance to ethanol.

P-64 - The effects of raphe lesions on the neuronal activity of the suprachiasmatic nucleus in rat hypothalamic slice preparation

P-64 - The effects of raphe lesions on the neuronal activity of the suprachiasmatic nucleus in rat hypothalamic slice preparation

Noradrenergic and serotonergic input necessary for imipramine-induced changes in beta but not S 2 receptor densities

Chronic imipramine administration decreases the density of serotonin S 2 and β-adrenergic receptors. The mode of action is not clear but might be assumed to be a result of imipramine interacting with its high affinity binding sites on presynaptic serotonin neurons. To investigate this possibility and the role of the serotonergic and noradrenergic systems on imipramine-induced receptor down- regulations, the effects of raphe lesions and 6-hydroxydopamine lesions were examined. The theory that imipramine acts through the serotonin system to down-regulate β-adrenergic receptors was supported by the observation that raphe lesions attenuated the impramine-induced β receptor denumeration. However, the effect of imipramine on the S 2 site may not be a result of serotonin uptake blockade. Raphe lesions which diminish 3H-imipramine high affinity binding did not alter the imipramine-induced decrease in S 2 receptor numbers. 6-Hydroxydopamine lesions prevented the reduction in β but not S 2 binding. Imipramine may exert its effect on S 2 binding through a site other than the high affinity, serotonin uptake site.

Effects of raphe lesions on circadian ACTH, corticosterone and motor activity rhythms in free-running blinded rats

Blinded female rats underwent additional midbrain raphe lesions, in order to explore the role of the raphe in the organization of endogenous circadian rhythms for ACTH, corticosterone (B) and motor activity (MA). Amplitudes and mean levels of rhythms were depressed for ACTH and MA, with persistent free-running circadian periodicity for MA and, in several rats, for ACTH and B as well. Other rats exhibited split circadian and ultradian rhythmicity for ACTH and B, whereas others again displayed no detectable ACTH rhythmicity. These results are discussed in the light of the structure of circadian pacemaker systems.

Dopamine release from the rat substantia nigra in vitro. Effect of raphe lesions and veratridine stimulation

In order to eliminate the 5-hydroxytryptaminergic input to the substantia nigra lesions were placed in the dorsal and medial raphe nuclei in a number of rats. The release of exogenously applied [ 3H]dopamine from the partially denervated substantia nigra was determined in vitro and found to be very similar to the release observed from slices of control substantia nigra. These results lend further support to the theory that the release of exogenously applied [ 3H]dopamine at the level of the substantia nigra occurs mainly from dopaminergic dendrites, rather than from terminals of 5-hydroxytryptamine-containing neurons. A veratridine-induced release of [ 3H]dopamine from the pars reticulata of the substantia nigra is also described. An almost complete blockade of veratridine (3.0 μM) stimulation was observed with 100 nM tetrodotoxin. Similar effects of veratridine and tetrodotoxin were also observed on [ 3H]dopamine release from slices of corpus striatum. These results suggest that dendrites of the dopaminergic neurones in the substantia nigra contain fast, tetrodotoxin-sensitive sodium channels.

Effect of raphe lesions on the circadian pattern of wheel running in the rat

In order to investigate whether a serotoninergic (5-HT) system might be involved in the regulation of the circadian pattern of wheel running in rats, the effect on running of ablation of the medial and dorsal raphe nuclei was studied. It was found that sham lesioned and dorsal raphe lesioned animals initially displayed reduced total daily running, although the animals returned to preoperative running levels by the end of testing. Throughout the entire period there was no effect upon the circadian distribution of running in the two groups. During the first week following surgery, however, the animals which had received both medial and dorsal raphe lesions were initially hyperactive, showing a 200% increase in running during the light period. For one week following surgery and then throughout the rest of the testing period the total amount of running of this group dropped below control levels while the circadian pattern of running returned to normal. These data suggest that although a 5-HT system projecting from the medial raphe may modulate the circadian pattern of running, the system is not essential and other neural components can compensate for the absence of this system.

Effect of raphe lesions on brain serotonin in the cat

A quantitative study of the regional distribution of serotonin (5-HT) in the forebrain, was performed in adult cats, following brainstem lesions. Seven to 10 days survival times were used to avoid nonspecific variations of the amine levels, as were observed in chronic preparations. Significant decreases of 5-HT levels were found after lesions of the nucleus centralis superior (CS), in hypothalamus, preoptic area, amygdala and hippocampus. After lesions of the nucleus dorsalis raphe (Dr), significant 5-HT decreases were also found in the hypothalamus and hippocampus. There was no change of 5-HT levels after lesions placed in the lateral midbrain, pontine tegmentum, or caudal pontine raphe, contrary to that was reported for chronic lesioned cats. These results suggest that CS and Dr may integrate different serotonergic subsystems and, probably, each one of these subsystems is related to specific functional phenomena.

Habituation and sensitization of the rat startle response: Effects of raphe lesions

In the first experiment raphe lesioned, sham operated and nonoperated rats were presented with 150 tones (50 at each of 3 intensities) a day for 5 days. No differences were found among the groups in the rate of startle response habituation either within or between sessions. However, overall levels of startle were much greater following raphe lesions and a tone by tone analysis indicated that this was caused by heightened tone-elicited sensitization in the raphe group. Further tests of startle sensitization in Experiment 2 found the raphe group to be more sensitized than the other groups by loud tones and footshocks but not by different levels of background white noise. The results support the theory that repetitive stimulus exposure produces both habituation and sensitization and that different neural systems may underly these two processes.