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At least 865 records · Page 48Linked to original sources

PubMed1985

The pharmacology of the hypothermic response in mice to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). A model of presynaptic 5-HT1 function.

In the mouse, injection (subcutaneously) of the putative 5-HT1 agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), produced a dose-related hypothermia (ED50:0.36 mg/kg). A maximum response was elicited by intracerebroventricular (i.c.v.) injection of 8-OH-DPAT (3 micrograms) and almost abolished by lesion of 5-HT-containing terminals in the brain with 5,7-dihydroxytryptamine (5,7-DHT; i.c.v.) or long-term treatment with p-chlorophenylalanine. The response was unaltered by a range of neurotransmitter antagonists: prazosin (alpha1-adrenoceptor), idazoxan (alpha2-adrenoceptor), metoprolol (beta1-adrenoceptor), erythro-DL-1-(7-methylindan-4-yloxy)-3-isopropylamino-but an-2-ol (beta2-adrenoceptor), (-)propranolol or (+/-)pindolol (beta-adrenoceptor), flupenthixol (dopamine) or Ro 15-1788 (benzodiazepine binding site). Classical 5-HT antagonists (methysergide, metergoline, cinanserin and methiothepin) were either without effect or facilitated the response and the 5-HT2 antagonist, ritanserin was also without effect. In contrast, quipazine and haloperidol produced a dose-related antagonism of the response. Since the response was almost abolished by a lesion induced by 5,7-DHT and was antagonised by quipazine, which is known to antagonise presynaptic 5-HT function in vitro, it is suggested that the hypothermic response is due to 8-OH-DPAT acting as an agonist at a presynaptic 5-HT receptor, which also appears to be sensitive to butyrophenones (the antagonism elicited by haloperidol but not by flupenthixol). The hypothermic response of mice to 8-OH-DPAT, therefore, may provide a simple and convenient in vivo model in which to measure the function of the presynaptic 5-HT receptor.

5,7-Dihydroxytryptamine↗

PubMed1986

Pharmacological analysis of the behavioural and thermoregulatory effects of the putative 5-HT1 receptor agonist, RU 24969, in the rat.

The roles of recognition sites for central neurotransmitters in the mediation of the behavioural effects of the putative 5-hydroxytryptamine (5-HT1) receptor agonist, RU 24969 [5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole] in the rat have been examined. The drug RU 24969 was found to have high affinity for 5-HT1A and 5-HT1B recognition sites. Hyperlocomotion, induced by RU 24969, was enhanced in animals depleted of 5-HT with 5,7-dihydroxytryptamine, suggesting an involvement of 5-HT receptors in the mediation of this behaviour. However, results of experiments with 5-HT receptor antagonists argued against the receptors being of either the 5-HT1 or 5-HT2 type. Despite the negligible affinity of RU 24969 for catecholamine receptors, hyperlocomotion induced by RU 24969 was clearly dependent on intact catecholamine systems. When hyperlocomotion was blocked by treatment with reserpine, reciprocal forepaw-treading and a flat body posture, behavioural responses which are consistent with activation of the putative 5-HT1A receptor, became evident. When animals were restrained from moving, RU 24969 dose-dependently reduced body temperature, an effect that may also be associated with activation of the 5-HT1A recognition site. Thus, although the mechanism by which RU 24969 induces hyperlocomotion is not yet established, the agonist nevertheless can induce functional responses consistent with its high affinity for the 5-HT1A recognition site.

5,7-Dihydroxytryptamine↗

PubMed1986

Nigrostriatal dopamine actions on the D2 receptors mediate methamphetamine effects on the striatonigral substance P system.

Multiple administrations of methamphetamine to rats produced elevated concentrations of substance P-like immunoreactivity within the substantia nigra, an effect which is believed to be mediated by increases in dopaminergic activity induced by methamphetamine. The results reported here demonstrate that the effect of methamphetamine is mediated specifically by the dopamine pathway in the nigrostriatum. Thus, extensive destruction of dopamine neurons in the nigrostriatum by lesions induced by 6-hydroxydopamine or blockade of synthesis of dopamine with alpha-methyl-p-tyrosine prevented the increases in substance P-like immunoreactivity in the nigra, induced by methamphetamine. Similarly, the concurrent administration of the D2 receptor antagonist, sulpiride, also prevented the effects of methamphetamine on substance P-like immunoreactivity in a dose-dependent way. In addition, multiple administrations of the D2 agonist, RU24926, elevated, whereas the DI agonist, SKF38393, decreased the content of substance P-like immunoreactivity in the nigra. The effects of methamphetamine were not altered in rats with lesions induced by 5,7-dihydroxytryptamine. Thus, these findings suggest that the effect of methamphetamine on the striatonigral substance P pathway is mediated by nigrostriatal dopaminergic actions on D2 receptors.

5,7-Dihydroxytryptamine↗

PubMed1987

Serotonin mediates cardiovascular responses to acetylcholine, bradykinin, angiotensin II and norepinephrine in the lateral septal area of the rat brain.

The infusion of acetylcholine, bradykinin, angiotensin II, norepinephrine and serotonin into the lateral septal area produced a dose-dependent increase of arterial blood pressure and heart rate. A pattern of inhibition of these cardiovascular responses, produced by pretreatment of the lateral septal area with phentolamine, 6-hydroxydopamine, methysergide and 5,7-dihydroxytryptamine was disclosed. These results suggest that the effects of acetylcholine, bradykinin and partially of angiotensin II, depend on the release of norepinephrine and the actions of this neurotransmitter in turn depend on the integrity of the serotonergic system in the lateral septal area.

5,7-Dihydroxytryptamine↗

PubMed1988

Emesis induced by 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343): evidence for a predominant central muscarinic M1 mediation.

The emetic action of 4-(m-chlorophenylcarbamoyloxy)-2- butynyltrimethylammonium chloride (McN-A-343) was investigated in the unanaesthetized cat, after it was injected into the cerebral ventricles, through chronically-implanted cannulae. Intracerebroventricular injection of McN-A-343 produced dose-dependent and shortlasting emesis, which was not completely abolished after ablation of the area postrema. The predominantly selective muscarinic M1 antagonist, pirenzepine as well as the mixed muscarinic M1 and M2 antagonist, atropine, injected into the cerebral ventricles, attenuated or abolished the emesis evoked by intracerebroventricular McN-A-343. Both atropine and pirenzepine produced dose-dependent inhibition of the emesis evoked by McN-A-343. However, the ID50 value for atropine was approximately five times greater than that for pirenzepine. Abolition of McN-A-343-induced emesis only occurred with the largest dose of atropine (1 mg). On the other hand, selected ganglionic blocking agents, an alpha- and beta-adrenoceptor blocking agent, a dopamine antagonist, a 5-hydroxytryptamine antagonist and an antihistamine, all injected into the cerebral ventricles, had no significant effect on emesis evoked by McN-A-343, similarly injected. The emetic response to intracerebroventricular injection of McN-A-343 was attenuated or abolished in cats pretreated with hemicholinium-3, triethylcholine, reserpine and 6-hydroxydopamine, intracerebroventricularly. On the contrary, the emetic response to intracerebroventricular injection of McN-A-343 was not altered in cats pretreated with intracerebroventricular injections of bretylium, alpha-methyl-p-tyrosine and 5,6-dihydroxytryptamine. It is postulated that the emesis produced by McN-A-343, injected into the cerebral ventricles, is mediated through muscarinic M1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1988

8-Hydroxy-2-(di-n-propylamino) tetralin, a selective serotonin1A receptor agonist, blocks haloperidol-induced catalepsy by an action on raphe nuclei medianus and dorsalis.

The selective serotonin1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was studied for its ability to reverse haloperidol-induced catalepsy in rats. Given subcutaneously 8-OH-DPAT (0.06-0.5 mg/kg), dose-dependently antagonized the catalepsy induced by 1 mg/kg of haloperidol. Intraventricular injection of the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), which caused marked depletion of 5-HT in brain, did not change haloperidol-induced catalepsy per se, but completely antagonized the anticataleptic effect of subcutaneously administered 8-OH-DPAT. When injected directly into the median or dorsal raphe nucleus, 8-OH-DPAT, in doses ranging from 0.2 to 5 micrograms/0.5 microliter, reduced the catalepsy induced by haloperidol. The results suggest that the activation of 5-HT1A receptors, probably those located presynaptically on 5-HT-containing cell bodies, reduces the catalepsy induced by haloperidol.

5,7-Dihydroxytryptamine↗

PubMed1989

Involvement of spinal monoaminergic pathways in antinociception produced by substance P and neurotensin in rodents.

The antinociceptive effects of substance P and of neurotensin have been determined in rodents after depletion of serotonin (5-HT) or noradrenaline (NA) in the spinal cord. The antinociceptive effect of substance P, given intraventricularly, in rats and mice was blocked after depletion of 5-HT in the spinal cord with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or with the inhibitor of the synthesis of 5-HT, p-chlorophenylalanine (PCPA), but not after depletion of NA in the spinal cord with the neurotoxin 6-hydroxydopamine (6-OHDA). Conversely, the antinociceptive effect of neurotensin in mice was blocked after lesion of spinal NA pathways with 6-OHDA. When 5-HT spinal pathways of mice were lesioned with 5,7-DHT, neurotensin-induced antinociception was blocked 7 but not 15 days after the lesion. p-Chlorophenylalanine failed to prevent this effect of neurotensin. The results suggest that the antinociceptive effect of substance P depends on the integrity of spinal 5-HT neurones, whereas that of neurotensin depends on spinal NA neurones and, only to a limited extent, on 5-HT neurones. It seems that different descending systems are involved in the antinociception elicited by these two neuropeptides.

5,7-Dihydroxytryptamine↗

PubMed1991

8-Phenyltheophylline reverses the antinociceptive action of morphine in the periaqueductal gray.

Morphine was injected into the periaqueductal gray region of the rat and 8-phenyltheophylline, an adenosine receptor antagonist, was injected intrathecally 15 or 30 min later, to determine whether supraspinally-administered morphine activated descending mechanisms to release adenosine (or a nucleotide which is metabolized to adenosine) from the spinal cord. 8-Phenyltheophylline (10 micrograms) reversed the antinociceptive action of morphine in the hot plate but not the tail-flick test. A combination of methysergide/phentolamine (15 micrograms each) reversed the action of morphine in both tests. 8-Phenyltheophylline retained the ability to reverse the action of morphine in the hot plate test in rats pretreated with 6-hydroxydopamine (to induce degeneration of descending noradrenergic pathways) but reversal was no longer observed in rats pretreated with 5,7-dihydroxytryptamine (after pretreatment with desipramine, to induce degeneration of descending serotonergic pathways). These results indicate that a component of the supraspinal antinociceptive action of morphine is due to release of adenosine or nucleotide, within the spinal cord and this release is dependent on intact serotonergic pathways.

5,7-Dihydroxytryptamine↗

PubMed1992

Role of serotonin and catecholamines in brain in the feeding suppressant effect of fluoxetine.

The hypophagic effect of fluoxetine was studied in rats, injected intracerebroventricularly with 150 micrograms/20 microliters 5,7-dihydroxytryptamine, to destroy serotonin-containing neurones or 250 micrograms/20 microliters 6-hydroxydopamine, to destroy catecholamine-containing neurones. The effect of various serotonin receptor antagonists was assessed as well. Neither neurotoxin significantly modified the effect of 20 mg/kg (i.p.) fluoxetine on food intake. Metergoline (1-5 mg/kg), (-)-propranolol (16 mg/kg) and ICS 205-930 (0.1 and 1 mg/kg) did not modify the hypophagic effect of fluoxetine, while mianserin (1 and 5 mg/kg), ritanserin (0.5 and 1 mg/kg) and xylamidine (3 mg/kg) slightly but significantly reduced it. While the mechanism by which some 5-HT receptor antagonists modify the effect of fluoxetine remains to be elucidated, it seems clear that 5-HT receptors hardly have any significant role in the ability of the drug to suppress food intake.

5,7-Dihydroxytryptamine↗

PubMed1992

Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism.

The effect of various doses of tianeptine on the extracellular concentrations of dopamine was studied in the striatum and nucleus accumbens of the rat. At 5 (but not 2.5) mg/kg intraperitoneally, tianeptine increased the extracellular dopamine only in the nucleus accumbens. At 10 mg/kg, the effect was also seen in the striatum but it was less marked and shorter-lasting. At 10 mg/kg (i.p.), tianeptine significantly raised the extracellular concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in both regions. The effect of 10 mg/kg tianeptine on dopamine and its metabolites was not significantly changed in animals which had received this dose twice daily for 15 days. Intracerebroventricular administration of 150 micrograms/20 microliters 5,7-dihydroxytryptamine, which markedly depleted serotonin in the brain, did not modify the effect of 10 mg/kg tianeptine on the extracellular concentrations of dopamine and HVA in the nucleus accumbens but reduced the effect on DOPAC. Various doses of tianeptine (1, 3 and 10 mg/kg i.p.) did not change the synthesis of serotonin and dopamine in the striatum and nucleus accumbens. The results show that tianeptine increased the extracellular concentrations of dopamine more in the nucleus accumbens than in striatum. The effect on the output of DA in the nucleus accumbens could be involved in the antidepressant activity of tianeptine.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1982

Locomotor activity and ingestive behavior after damage to ascending serotonergic systems.

The effects of electrolytic midbrain raphe lesions on ingestive behavior and locomotor activity of rats were compared to those produced by intracerebral injections of 5,7 dihydroxytryptamine (5,7 DHT) at various points along the ascending serotonergic pathways. Only electrolytic lesions of the median and/or dorsal raphe nuclei produced significant changes in food intake, water intake, body weight gain, and wheel running activity. Intracerebral injections of 5,7 DHT, a selective serotonergic neurotoxin, had no effect on any of these variables. However, 5,7 DHT induced lesions produced decreases in forebrain synaptosomal uptake of serotonin which were equivalent to, or greater than, those resulting from electrolytic lesions of the midbrain raphe nuclei. Failure of 5,7 DHT injections to replicate the behavioral changes resulting from electrolytic lesions of the midbrain raphe nuclei suggests that loss of ascending serotonergic projections was not responsible for the behavioral effects that followed the electrolytic lesions.

5,7-Dihydroxytryptamine↗

PubMed1980

Prolonged stimulation of respiration by endogenous central serotonin.

We have recently reported a new neural brainstem mechanism which is uniquely activated by stimulation of carotid body afferent input to the brain and which facilitates respiration for hours after the immediate affects of the stimulation have dissipated (Millhorn, Eldridge and Waldrop, 1980). In the present study respiratory responses to carotid body or carotid sinus nerve stimulation were measured in vagotomized, anesthetized, and paralyzed cats whose end-tidal PCO2 and temperature were servo-controlled and kept constant. The responses of animals pretreated with various serotonin antagonists and a dopamine-norepinephrine antagonist were compared to the responses of untreated control animals. All three differently acting serotonin antagonists (methysergide, parachlorophenylalanine, and 5, 7-dihydroxytryptamine) either prevented or significantly reduced the magnitude of the long-lasting respiratory response whereas the dopamine-norepinephrine antagonist (alpha-methyltyrosine) failed to alter it. We conclude that the long-lasting increase of respiratory activity following stimulation of carotid body afferents is due to activation of an endogenous central serotoninergic mechanism which facilitates respiration.

5,7-Dihydroxytryptamine↗

PubMed1987

Serotonin containing neurons in the retina of the teleost Eugerres plumieri.

The concentration and localization of serotonin was determined in the retina of the teleost Eugerres plumieri by using high performance liquid chromatography (HPLC) and immunohistochemical techniques. Serotonin and dopamine were measured simultaneously, their concentrations in the retina being 77 +/- 8 and 516 +/- 23 ng/mg tissue respectively. Treatment of the animals with pargyline significantly increased the levels of dopamine and serotonin. When retinas were treated with the neurotoxin 5,6-dihydroxytryptamine, the level of serotonin was reduced by more than 90% while the dopamine content only diminished by 20% when compared to controls. By using immunohistochemistry with a monoclonal anti-serotonin antibody it was possible to localize this amine in cell bodies of a population of amacrine cells with processes extending mainly into a thin layer of the most external lamina of the inner plexiform layer. Very few ramifications were seen projecting to the internal lamina of this layer. When visualized in flat mount preparations, dense arborization of fluorescent processes was observed. This is the first direct evidence that serotonin is apparently present in amacrine cells of the retina of E. plumieri with a distribution of the serotonergic terminals similar to goldfish but somewhat different when compared to other species.

5,6-Dihydroxytryptamine↗

PubMed1979

Neurochemical basis of the dorsal bundle extinction effect.

Injection of 6-hydroxydopamine into the mesencephalon of the rat has been found to cause resistance to extinction on continuously reinforced schedules. The neurochemical basis of this effect was investigated by using another concentration of 6-hydroxydopamine and by another position of injection. Severe depletion of forebrain noradrenaline was found after these injections with no change in dopamine, serotonin, cholinergic or GABAergic parameters in any brain area measured. The noradrenergic nature of the effect was further shown by the reversal fo the usual behavioural effect following pretreatment with a noradrenaline uptake inhibitor (desimipramine, 25 mg/kg 30 min prior to intracerebral injection of 6-hydroxydopamine). This rules out non-specific damage caused by the 6-hydroxydopamine as the neurochemical basis of the dorsal bundle extinction effect. Failure to find resistance to extinction after either kainic acid or 5-7 dihydroxytryptamine injection seems also to exclude respectively cell body loss at the injection site or damage to serotonergic systems. It is concluded that the dorsal bundle extinction effect is noradrenergic in nature.

5,7-Dihydroxytryptamine↗

PubMed1979

Morphine potentiation of tonic immobility: effects of naloxone, PCPA, and 5,6-DHT.

The duration of tonic immobility in chickens, a catatonic-like state produced by brief restraint, was greatly potentiated by a single 1.0 mg/kg injection of morphine. Naloxone by itself, however, had no effect on tonic immobility, and only an exceptionally large dose of naloxone blocked the morphine potentiation. Pretreatment with PCPA and 5,6-dihydroxytryptamine completely eliminated the morphine enhancement. The effect of morphine on tonic immobility may be mediated by a central serotonergic-raphe system.

5,6-Dihydroxytryptamine↗

PubMed1980

Effects of nomifensine and desipramine on the sequelae of intracerebrally-injected 6-OHDA and 5,6-DHT.

Pretreatment with either nomifensine or desipramine (15 mg/kg) attenuated the depletion of forebrain noradrenaline induced by unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. Neither pretreatment influenced the depletions of striatal dopamine induced by medial forebrain bundle lesions with 6-hydroxydopamine or 5,6-dihydroxytryptamine, or contralateral rotational responses to apomorphine in the 6-hydroxydopamine-lesioned animals. Pretreatment with nomifensine attenuated the depletion of striatal dopamine induced by intrastriatal injections of 6-hydroxydopamine, consistent with inhibition of dopamine uptake in vivo. Nomifensine may differently influence distinct axonal and terminal uptake mechanisms for dopamine.

5,6-Dihydroxytryptamine↗

PubMed1980

On the neurochemical basis of self-stimulation with midbrain raphe electrode placements.

Bar-pressing for electrical stimulation of the median raphe nucleus in rats was not attenuated by 5HT receptor blockade with metergoline or cyproheptadine, by 5HT depletion induced with parachloroamphetamine or by prior destruction of ascending 5HT pathways with intracerebral microinjections of 5,7-dihydroxytryptamine. Furthermore, in a shuttle box paradigm in which rats could both initiate and terminate stimulation, parachlorophenylalanine did not antagonize initiation of stimulation. It is concluded that the rewarding effects of raphe stimulation are not mediated by serotonergic mechanisms. In contrast to these results, alpha-methyl-paratyrosine induced catecholamine depletion exerted an inhibitory effect on initiation behaviour without impairing termination of stimulation. It is concluded that the rewarding component of raphe stimulation is mediated by catecholamines. Termination of (escape from) stimulation was not materially affected by catecholamine or 5HT depletion suggesting the aversive component of raphe stimulation may not be mediated by these monoamines.

5,7-Dihydroxytryptamine↗

PubMed1980

The effect of serotonin depletion on the discriminability of LSD.

Nine groups of rats were trained to discriminate LSD (0.12 mg/kg) from saline in a two-lever, water-reinforced, drug discrimination procedure. After stable discriminative performance was obtained (>95% correct), groups were administered one of several treatments which lower the concentration of serotonin (5-HT) in brain: (1) 12.5, 25, 50, 100 or 200 microgram of 5,7-dihydroxytryptamine (5,7-DHT) intraventricularly (IVT); (2) 3 X 100 mg/kg of p-chlorophenylalanine (PCPA) intraperitoneally (IP); or (3) 20 mg/kg of p-chloroamphetamine (PCA) IP. Control rats received either IVT injections of 5,7-DHT vehicle or IP injections of PCA or PCPA vehicles. Beginning 12 days after treatment, lever preference following various doses of LSD was determined. The results indicated that only the 200 microgram dose of 5,7-DHT and PCPA caused a significant potentiation of LSD-lever responding at the 0.03 mg/kg dose of LSD while all treatments except 12.5 and 25 microgram of 5,7-DHT resulted in significant depletion of 5-HT. Moreover, amount of 5-HT and percent LSD responding following 0.03 mg/kg LSD were not significantly correlated. It was concluded that 5-HT depletion, per se, cannot account for supersensitivity to the behavioral effects of LSD.

5,7-Dihydroxytryptamine↗