RESUMEN
AIMS: The effect of i.p. injection or oral ingestion of glycinamide, a glycine pro-drug, on two tests for nociception was assessed in ovariectomized Sprague Dawley rats. MAIN METHODS: To explore the potential analgesic effect of glycinamide the vocalization threshold to tail shock (VT) and the tail flick latency (TFL) were used. Glycinamide was administered both through the intraperitoneal route (doses 0, 25, 100, 400, 800 mg/kg) and through ad libitum oral ingestion of glycinamide solution (40 mg/ml) following a 24h period of water deprivation. KEY FINDINGS: Glycinamide exerted a significant analgesic effect on VT when injected i.p. at doses of 400 or 800 mg/kg. Analgesia occurred 10-20 min post-injection and persisted approx 45 min. At the high dose level, glycinamide exerted a weaker and more delayed effect on TFL than on the VT test. I.p. injection of 800 mg/kg glycinamide inhibited vocalizations induced by the application of suprathreshold tail shocks (30% above threshold) with a latency of approx 3 min and duration of approx 1h. The volume of a glycinamide solution (40 mg/ml) ingested by rats deprived of water for 24h was positively correlated with the degree of analgesia in the VT test. Values between 100 and 200mg glycinamide exerted clear analgesic responses. SIGNIFICANCE: Thus, glycinamide, either by systemic or oral routes, exerts a clear analgesic effect in the VT test of nociception and a much weaker action in the TFL test. This effect is probably due to the conversion of glycinamide to glycine in the brain.
Asunto(s)
Analgésicos/farmacología , Glicina/análogos & derivados , Dolor Nociceptivo/tratamiento farmacológico , Administración Oral , Analgésicos/administración & dosificación , Animales , Relación Dosis-Respuesta a Droga , Femenino , Glicina/administración & dosificación , Glicina/farmacología , Inyecciones Intraperitoneales , Ovariectomía , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacos , Factores de TiempoRESUMEN
Brief vaginocervical stimulation using a glass rod (VCS) combined with manual flank-perineal stimulation (FS) rapidly (within 5 min) induced both receptive and proceptive behavioural responses to males in ovariectomised, oestrogen-primed rats. This receptive-proceptive response to males, resulting from a single brief (5-s duration) instance of manual VCS + FS, declined markedly within 4 h. However, the decline was prevented if the females were mounted by males immediately after the manual VCS + FS and 2 h later. We tested the participation of the cAMP-dependent protein kinase A system and the mitogen-activated protein kinase (MAPK) system in the response to VCS + FS by infusing either 100 ng of Rp-adenosine 3',5'-cyclic monophosphorothiate triethylamonium salt (a protein kinase A blocker) or 3.3 microg of PD98059 (a MAPK blocker) i.c.v. 15 min prior to VCS + FS. Both inhibitors blocked the ability of VCS + FS to induce the proceptive-receptive responses to males at all testing intervals. In experiment 2, systemic administration of 5 mg of RU486 1 h before VCS + FS also blocked the ability of VCS + FS to induce the proceptive-receptive responses to males. The present findings suggest that both VCS + FS and mating stimuli provided by males release neurotransmitters and neuromodulators that trigger the protein kinase A and the MAPK signalling systems, which interact with the progestin receptor to rapidly (within 5 min) induce proceptive-receptive behaviour in females.