cgs-12066b and alpha-methylserotonin

The effects of serotonergic agonists were examined in intact and spinal fetuses, using an in vivo fetal rat preparation. On Gestational Day 20, fetuses were prepared with a midthoracic or sham spinal transection. Dose-response curves were obtained for quipazine (nonselective 5-hydroxytryptamine [5-HT] agonist; 1.0-10.0 mg/kg), CGS-12066A (5-HT-sub(1B) agonist; 1.0-30.0 mg/kg), and alpha-methylserotonin (alpha-Me-5-HT; 5-HT-sub-2 agonist; 0.2-15.0 mg/kg). During a 10-min test, each of the agonists (delivered via intraperitoneal injection) influenced fetal behavior: They increased the occurrence of head movements, mouthing, and hindlimb stepping. Quipazine and alpha-Me-5-HT also promoted hindlimb activity in spinal fetuses. Thus, stimulation of the fetal 5-HT system modulates motor activity at multiple levels of the developing central nervous system.

Topics: Analysis of Variance; Animals; Behavior, Animal; Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Hindlimb; Male; Motor Activity; Pregnancy; Psychomotor Performance; Quinoxalines; Quipazine; Rats; Rats, Sprague-Dawley; Serotonin; Serotonin Receptor Agonists; Spinal Cord Injuries

1. In the present study, we analysed the effect of different doses of 5-hydroxytryptamine (5-HT; intravenous infusions of 0.001-40 microg/kg per min) in the autoperfused hindquarters of the rat subjected to electrical stimulation (frequencies of 0.5-20 Hz) of the lumbar chains, investigating the relationship between the adrenergic and serotonergic systems in this vascular bed. 2. Because we observed that 5-HT inhibited the increases in perfusion pressure induced by electrical stimulation of the lumbar chains, we used different agonists and antagonists to analyse the mechanism of action of 5-HT. 3. The effect of 5-HT was inhibited by methiothepin (a non-specific 5-HT receptor antagonist), but not by ritanserin (a selective 5-HT2 receptor antagonist). The effects of 5-HT were mimicked by 5-carboxamidotryptamine (a 5-HT1 receptor agonist) and L-694 247 (a selective 5-HT1D receptor agonist), but not by 8-hydroxy-2-dipropylaminotetralin (a 5-HT1A receptor agonist), CGS-12066B (a 5-HT1B receptor agonist), alpha-methyl-5-HT (a 5-HT2 receptor agonist), 1-(3-chlorophenyl) piperazine (a 5-HT2C receptor agonist) or 1-phenylbiguanide (a 5-HT3 receptor agonist). The selective 5-HT1D/1B receptor antagonist BRL 15572 inhibited the effect of the agonist L-694 247. 4. Our data suggest that 5-HT inhibits the increases in perfusion pressure induced by the electrical stimulation of the lumbar chains, acting on presynaptic 5-HT1D receptors and decreasing the release of noradrenaline from the sympathetic nerves in the hindquarter vascular bed of the rat.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Biguanides; Biphenyl Compounds; Dose-Response Relationship, Drug; Electric Stimulation; Hindlimb; In Vitro Techniques; Infusions, Intravenous; Male; Methiothepin; Oxadiazoles; Perfusion; Piperazines; Pressure; Quinoxalines; Rats; Rats, Wistar; Ritanserin; Serotonin; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT2 Receptor Agonists; Serotonin 5-HT3 Receptor Agonists; Serotonin Agents; Serotonin Antagonists; Serotonin Receptor Agonists; Tryptamines; Vasoconstriction

Whole cell patch-clamp recordings were obtained from projection neurons and interneurons of the rat basolateral amygdala (BLA) to understand local network interactions in morphologically identified neurons and their modulation by serotonin. Projection neurons and interneurons were characterized morphologically and electrophysiologically according to their intrinsic membrane properties and synaptic characteristics. Synaptic activity in projection neurons was dominated by spontaneous inhibitory postsynaptic currents (IPSCs) that were multiphasic, reached 181 +/- 38 pA in amplitude, lasted 296 +/- 27 mS, and were blocked by the GABAA receptor antagonist, bicuculline methiodide (30 microM). In interneurons, spontaneous synaptic activity was characterized by a burst-firing discharge patterns (200 +/- 40 Hz) that correlated with the occurrence of 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive, high-amplitude (260 +/- 42 pA), long-duration (139 +/- 19 mS) inward excitatory postsynaptic currents (EPSCs). The interevent interval of 831 +/- 344 mS for compound inhibitory postsynaptic potentials (IPSPs), and 916 +/- 270 mS for EPSC bursts, suggested that spontaneous IPSP/Cs in projection neurons are driven by burst of action potentials in interneurons. Hence, BLA interneurons may regulate the excitability of projection neurons and thus determine the degree of synchrony within ensembles of BLA neurons. In interneurons 5-hydroxytryptamine oxalate (5-HT) evoked a direct, dose-dependent, membrane depolarization mediated by a 45 +/- 6.9 pA inward current, which had a reversal potential of -90 mV. The effect of 5-HT was mimicked by the 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT), but not by the 5-HT1A receptor agonist, (+/-) 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), or the 5-HT1B agonist, CGS 12066A. In projection neurons, 5-HT evoked an indirect membrane hyperpolarization ( approximately 2 mV) that was associated with a 75 +/- 42 pA outward current and had a reversal potential of -70 mV. The response was independent of 5-HT concentration, blocked by TTX, mimicked by alpha-methyl-5-HT but not by 8-OH-DPAT. In interneurons, 5-HT reduced the amplitude of the evoked EPSC and in the presence of TTX (0.6 microM) reduced the frequency of miniature EPSCs but not their quantal content. In projection neurons, 5-HT also caused a dose-dependent reduction in the amplitude of stimulus evoked EPSCs and IPSCs. These results suggest that ac

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Amygdala; Animals; Bicuculline; Evoked Potentials; Excitatory Postsynaptic Potentials; GABA-A Receptor Antagonists; In Vitro Techniques; Interneurons; Male; Neurons; Patch-Clamp Techniques; Quinoxalines; Rats; Rats, Long-Evans; Receptor, Serotonin, 5-HT1B; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Serotonin; Serotonin Receptor Agonists; Synaptic Transmission; Tetrodotoxin

The changes in the latency for tail withdrawal in response to noxious heating of the skin induced by microinjection of opioid or serotonergic agonists into the anterior pretectal nucleus (APtN) was studied in rats. The mu-opioid agonist DAMGO (78 and 156 picomol), but not the delta-opioid agonist DADLE (70 and 140 pmol), the kappa-opioid agonist bremazocine (0.24 and 0.48 nanomol) or the sigma-opioid agonist N-allylnormetazocine (0.54 nanomol), produced a dose-dependent antinociceptive effect. The 5-HT1 agonist 5-carboxamidotryptamine (19 and 38 nanomol) and the 5-HT1B agonist, CGS 12066B (1.12 and 2.24 nanomol), but not the non-selective 5-HT agonist m-CPP (41 to 164 nanomol), 5-HT2 agonist alpha-methylserotonin (36 and 72 nanomol) and 5-HT3 agonist 2-methylserotonin (36 and 72 nanomol), produced a dose-dependent antinociceptive effect. These results indicate that the antinociceptive effects of opioid or serotonergic agonists microinjected into the APtN depend on drug interaction with local mu or 5-HT1B receptors, respectively.

Topics: Analgesics; Animals; Benzomorphans; Brain; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Male; Microinjections; Pain; Phenazocine; Piperazines; Quinoxalines; Rats; Rats, Wistar; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Serotonin; Serotonin Receptor Agonists