Behavioral and neurochemical alterations evoked by p-Chlorophenylalanine application in rats examined in the light-dark crossing test. (1/208)

The aim of the present study is to examine the effects of serotonin synthesis inhibition with p-Chlorophenylalanine (p-CPA) in rats on (1) anxiety behavior examined in the light-dark crossing test and, (2) regional brain concentration of monoamines (NA, DA and 5-HT) and their metabolites (MHPG, DOPAC, HVA and 5-HIAA) as well as GABA in the hypothalamus, amygdala, hippocampus, midbrain central gray matter and the frontal cortex. Treatment of animals with p-CPA produced a significant increase in time out from the illuminated part of the chamber and in time of locomotor activity in the illuminated part of the chamber. HPLC analysis showed a significant reduction of 5-HT and 5-HIAA concentration in all examined brain regions with the exception of the frontal cortex. Additionally, a significant decrease in DA and its metabolites, DOPAC and HVA occurred in the hypothalamus and amygdala. Moreover, we observed a significant decrease in frontal cortex NA concentration after p-CPA administration. The results of our study suggest that administration of p-CPA is effective in reduction of anxiety through depletion of 5-HT accompanied by diminution of catecholamines, especially DA and its metabolites in the main emotional brain regions.  (+info)

Sleep and serotonin: an unfinished story. (2/208)

Serotonin (5-HT) was first believed to be a true neuromodulator of sleep because the destruction of 5-HT neurons of the raphe system or the inhibition of 5-HT synthesis with p-chlorophenylalanine induced a severe insomnia which could be reversed by restoring 5-HT synthesis. However the demonstration that the electrical activity of 5-HT perikarya and the release of 5-HT are increased during waking and decreased during sleep was in direct contradiction to this hypothesis. More recent experiments suggest that the release of 5-HT during waking may initiate a cascade of genomic events in some hypnogenic neurons located in the preoptic area. Thus, when 5-HT is released during waking, it leads to an homeostatic regulation of slow-wave sleep.  (+info)

Receptors and neurotransmitters involved in the dual modulation of prolactin release by the serotoninergic system in pregnant and lactating rats. (3/208)

The receptors and neurotransmitter pathways that may participate in the inhibitory action of 5-hydroxytryptamine (5HT) on prolactin release during late pregnancy and lactation in rats were studied. Administration of the 5HT synthesis inhibitor, p-chlorophenylalanine, to late pregnant rats induced a significant increase in serum prolactin concentrations at 17:00 h on day 19 of pregnancy that was partially blocked by injections of the 5HT precursor, 5-hydroxytryptophan, or the 5HT agonists, 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (S1a), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (S2) and N-(3-chlorophenyl)imidodicarbonimide diamide HCl (S3), but not by RU 24969 (S1b) or 1-meta-(chlorophenyl)-piperazine-2-HCl (S1a-2c). The 5HT neurotoxins, fenfluramine and p-chloroamphetamine, which selectively destroy fine axon serotoninergic fibres but not coarse ones, prevented the increase in circulating prolactin observed at 18:00 h on pro-oestrus and on day 21 of pregnancy, but did not modify serum prolactin concentrations at 17:00 h on day 19 of pregnancy. Administration of the adrenergic antagonists, metoprolol or prazosin, also prevented the stimulatory effects of p-chlorophenylalanine or ketanserin in pregnant rats on day 19 (17:00 h) or on days 10-12 (16:30 h) in lactating rats separated from their litters. Administration of p-chlorophenylalanine to pregnant rats on day 19 reduced dopamine concentrations in the arcuate nucleus and in the anterior hypothalamus and noradrenaline concentrations in the anterior hypothalamus and the suprachiasmatic nucleus. These results indicate that the inhibitory actions of 5HT on prolactin release in pregnant and lactating rats are mediated by S1a, S2a and S3 receptors and by the coarse axon serotoninergic fibres. In addition, the inhibitory actions of 5HT may modulate the action of a stimulatory adrenergic pathway, as well as the concentrations of noradrenaline and dopamine in different hypothalamic areas, which, in turn, particularly arcuate nucleus dopamine, regulate prolactin release.  (+info)

Serotonin depletion and barrel cortex development: impact of growth impairment vs. serotonin effects on thalamocortical endings. (4/208)

Converging evidence supports a role of serotonin (5-hydroxytryptamine; 5-HT) in barrel cortex development. Systemic administration of 5-HT-depleting drugs reduces cross-sectional whisker barrel areas in the somatosensory cortex (SSC) of neonatal rats. Here we assess the relative impact on barrel pattern formation of (i) 5-HT depletion and (ii) decreased brain growth, which is often associated with pharmacological 5-HT depletion, by comparing the effects of 5-HT-depleting drugs with those of reduced protein intake. Left hemisphere 5-HT levels in the SSC and right hemisphere whisker barrel areas were assessed at postnatal day 6 (P6) in the same animal following injection of p-chloroamphetamine (PCA) or p-chlorophenylalanine (PCPA) at P0. Both drugs significantly reduced cortical 5-HT content and mean barrel areas at P6, but also body and brain growth. Differences in brain weight accounted for 84.4% of the variance in barrel size, with negligible contributions by cortical 5-HT content. PCPA-treated animals sacrificed at P14 yielded similar trends, albeit less pronounced. Finally, reduced protein intake resulted in lower body weight and cortical 5-HT levels at P6, but yielded no change in brain weight or mean barrel area. Barrel formation therefore appears markedly less sensitive to 5-HT depletion per se than to drug-induced growth impairment.  (+info)

Cisplatin-induced early and delayed emesis in the pigeon. (5/208)

1. Intravenously injected cisplatin at a dose of 4 mg kg(-1) induced early and delayed emesis in all pigeons without occurrence of lethality during a 72 h observation period. The early emetic response occurred with a latency of 81.3+/-8.0 min (n=15) and reached a peak at 2 - 3 h, and decreased gradually within 8 h after injection. Then the delayed emetic response, whose peak was found between 10 to 23 h, lasted up to 48 h. The emetic response markedly declined after 48 h. 2. Reserpine markedly reduced monoamine levels in both brain and intestine and completely abolished the early and delayed emesis. Dexamethasone markedly reduced not only the early but also the delayed emetic responses. p-Chlorophenylalanine decreased the level of serotonin in brain and intestine without affecting noradrenaline and dopamine and partly reduced the early emetic response, but did not affect delayed emesis. 3. Bilateral vagotomy prolonged the latency time to the onset of early emesis, and reduced the emetic responses in both the early and delayed phases. 4. The above results suggest that the cisplatin-induced early emesis in the pigeon is partially mediated via the vagal nerve and reserpine-sensitive monoaminergic systems including the serotonergic system; the delayed emesis is associated with monoaminergic but not the serotonergic systems.  (+info)

Endogenous 5-HT tonically inhibits spontaneous firing activity of dorsal hippocampus CA1 pyramidal neurons through stimulation of 5-HT(1A) receptors in quiet awake rats: in vivo electrophysiological evidence. (6/208)

The present study was performed to examine an overall effect of endogenous serotonin (5-HT) on the spontaneous firing activity of the dorsal hippocampus CA1 pyramidal neurons in quiet awake rats. A selective 5-HT(1A) antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide (WAY-100635: 0.03-0.2 mg/kg, s.c.) significantly increased the firing activity. A depletion of 5-HT with parachlorophenylalanine (PCPA: 500 mg/kg/day x 3 days) completely abolished this increasing effect of WAY-100635. The baseline spike frequency of the PCPA-treated rats (3.90 +/- 0.39 Hz) was significantly higher than that of the vehicle-treated rats (2.09 +/- 0.19 Hz). A 5-HT(2A) antagonist ritanserin (1 mg/kg, i.p.) and a 5-HT(3/4) antagonist 2-methoxy-4-amino-5-chloro benzoic acid 2-(diethylamino) ethyl ester (SDZ-205557: 3 mg/kg, s.c.) did not modify the firing activity and the increasing effect of WAY-100635. These results suggest that, in quiet awake rats, endogenous 5-HT would tonically inhibit the spontaneous firing activity of the CA1 pyramidal neurons mainly through stimulating 5-HT(1A) receptors.  (+info)

Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nitric oxide synthase. (7/208)

Genetically engineered mice with targeted disruption of the neuronal nitric oxide synthase (nNOS) gene established the inhibitory role of nitric oxide (NO) in male impulsive aggressive behavior. This was later confirmed by using selective nNOS inhibitors in male wild-type mice. The molecular mechanisms accounting for the aggressive behavior caused by the lack of neuronally derived NO is not known. Recent studies suggest that central serotonergic neuronal circuits and particularly 5-HT(1A) and 5-HT(1B) receptors play a prominent role in the regulation of aggression. Accordingly, we investigated whether the aggressiveness caused by the lack of nNOS might be because of alterations in serotonergic function. We now demonstrate that the excessive aggressiveness and impulsiveness of nNOS knockout mice is caused by selective decrements in serotonin (5-HT) turnover and deficient 5-HT(1A) and 5-HT(1B) receptor function in brain regions regulating emotion. These results indicate an important role for NO in normal brain 5-HT function and may have significant implications for the treatment of psychiatric disorders characterized by aggressiveness and impulsivity.  (+info)

Reduced brain serotonin activity disrupts prepulse inhibition of the acoustic startle reflex. Effects of 5,7-dihydroxytryptamine and p-chlorophenylalanine. (8/208)

These experiments examined the impact of extensive depletions of forebrain 5-hydroxytryptamine (5-HT; serotonin) levels on prepulse inhibition (PPI) of the acoustic startle reflex in rats. In Experiment 1, injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal and median raphe nuclei disrupted PPI. This deficit was observed beginning 2 days after lesioning and was still apparent 8 weeks later. Basal startle reactivity was not altered. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.1 mg/kg) and the dopamine receptor agonist apomorphine (1mg/kg) also disrupted PPI; the effect of 8-OH-DPAT, but not apomorphine, was potentiated in 5-HT-depleted rats. Basal startle reactivity was enhanced by 8-OH-DPAT in sham-lesioned rats but not in 5,7-DHT-lesioned rats. In Experiment 2, a second method for depleting 5-HT was used. The tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA) also disrupted PPI without altering basal startle reactivity. Again, 8-OH-DPAT disrupted PPI in control animals; this effect was not altered in PCPA-treated rats but the increase in basal startle reactivity induced by 8-OH-DPAT was not observed in PCPA-treated rats. Taken together with the results of previous experiments involving drugs that enhance 5-HT neurotransmission it appears that both increases and decreases in 5-HT activity disrupt PPI.  (+info)