The effect of L-dopa on neuroleptic-induced catalepsy.
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1. The anterior horn of one lateral ventricle was perfused in anaesthetized cats treated with inhibitors of monoamine oxidase, and the effluent was tested for 5-hydroxytryptamine (5-HT).2. The basal release of 5-HT varied from 0.25 to 4 ng in 25 min, and was usually about 1 ng.3. The basal release rose and fell with body temperature.4. Electrical stimulation for 15 min of the nucleus linearis intermedius or of the nucleus linearis rostralis caused a release of 5-HT which rarely outlasted the collection period of 25 min.5. Low frequencies (0.5/sec) were, per stimulus, more effective than high frequencies in releasing 5-HT. Over a 15 min period of stimulation, however, the highest total yield was at 20/sec; it fell abruptly at still greater frequencies.6. No release was obtained if the stimulating electrode was positioned in a variety of brain structures outside the two linear nuclei.7. The experiments indicate that 5-HT acts as a transmitter of impulses in neurones originating in the linear nuclei and terminating in caudate nucleus and septum.
The nucleus linearis intermedius raphe and the nucleus linearis rostralis were stimulated during the perfusion of the anterior horn of the right lateral ventricle of anaesthetized cats. Whereas release of 5-hydroxytryptamine (5-HT) was consistently obtained, there was no release of acetylcholine (ACh). The independence of the release of 5-HT from that of ACh was seen both during low basal release of ACh (rising base line), and during the period when a plateau of resting release had been reached. It was also demonstrated in experiments in which the same perfusate was examined for both compounds.
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Evidence from the present study suggests that activation of both 5-HT(1A) and 5-HT(4) (5-hydroxytryptamine) receptor subtypes stimulates cyclic adenosine monophosphate (cAMP) synthesis in cultured embryonic mouse mandibular mesenchymal cells (micromass cultures). When these cells were grown in serum-free medium and treated with 10(-8) M agonist selective for either the 5-HT(1A) or 5-HT(4) receptor subtype (8-OH-DPAT and SC53116, respectively), this significantly stimulated cAMP synthesis and increased insulin-like growth factor I (IGF-I), but not IGF-II, protein levels compared to vehicle-treated controls, as measured by semi-quantitative immunobinding assays. Consistent with these results, IGF-I was significantly decreased when mandibular mesenchymal cells were grown in serum-containing medium (which contains micromolar amounts of 5-HT from fetal calf serum) and treated with 10(-8) M antagonist selective for the 5-HT(1A) or 5-HT(4) receptor subtype (NAN-190 on SDZ-205,557). Forskolin also stimulated cAMP and IGF-I (but not IGF-II) in both serum-containing and serum-free cultures. These results indicate that activation of 5-HT receptors that increase cAMP promotes synthesis of IGF-I. This may occur by activation of the cAMP response element sequence present in the IGF-I promoter region. Stimulation of the adenylyl cyclase pathway by activation of 5-HT(1A) or 5-HT(4) receptors may be one mechanism by which serotonin regulates IGF-I synthesis in developing craniofacial mesenchymal cells.
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