RESUMEN
To examine the relationship between glutamate receptors and the action of NC-1900 on a step-through passive avoidance (PA) task in mice, MK-801, an NMDA receptor blocker, and (S)-4-carboxyphenylglycine (4CPG), a group I metabotropic receptor antagonist, were administered intraventricularly (i.c.v.) singly or as co-injections. The i.c.v. injection of MK-801 (0.8 microg) or 4CPG (2 microg) decreased the latency on the PA task. NC-1900 (1 ng/kg, subcutaneously (s.c.)) alone prolonged the latency on the retention trial in the PA task. MK-801 (0.2 and 0.8 microg) or 4CPG (0.5 and 2 microg) significantly inhibited the action of NC-1900, while the s.c. injection of NC-1900 did not affect latency in mice that received i.c.v. co-injection of MK-801 and 4CPG at any of the doses tested. These results suggest that glutamate receptors participate in the action of NC-1900 on learning and memory in PA task performance.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Memoria/efectos de los fármacos , Oligopéptidos/antagonistas & inhibidores , Ácido Pirrolidona Carboxílico/análogos & derivados , Animales , Benzoatos/farmacología , Maleato de Dizocilpina/farmacología , Ácido Glutámico/fisiología , Glicina/análogos & derivados , Glicina/farmacología , Masculino , Ratones , N-Metilaspartato/farmacología , Ácido Pirrolidona Carboxílico/antagonistas & inhibidores , Receptores de Glutamato/efectos de los fármacos , Vasopresinas/antagonistas & inhibidoresRESUMEN
To examine the effect of the arginine-vasopressin fragment, [pGlu(4),Cyt(6)]AVP((4-9)) (AVP4-9), on group II metabotropic glutamate receptor (mGluR2/3) agonist and antagonist induced impairment of passive avoidance (PA) task performance, AVP4-9 or phorbol 12-myristate 13-acetate (PMA) was administered in the presence of mGluR2/3-related drugs that induced the impairment of the step-through-type PA task performance. The PA task performance was evaluated in terms of the latency (the time that elapsed prior to entry into the dark compartment) at 24 h after the electrical stimulation. The subcutaneous injection of AVP4-9 at 1 mug/kg had the greatest facilitative effect on the performance, and the facilitative effect of AVP4-9 was inhibited by NPC-15437, a specific protein kinase C (PKC) inhibitor. The injection of AVP4-9 ameliorated PA task performance impairment induced by DCG-IV, an mGluR2/3 agonist. Intracisternal injection of PMA, a PKC activator, also ameliorated the DCG-IV-induced impairment. High doses of AVP4-9 exacerbated the PA task performance impairment induced by LY341495 (an mGluR2/3 antagonist), and PMA injection (1 mug) also exacerbated the impairment induced by the antagonist. These results suggest that an increase in the activity of the PKC-signaling pathway may not always facilitate PA task performance; therefore, AVP4-9 can either enhance or inhibit memory performance in mice.
Asunto(s)
Aminoácidos/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Memoria/efectos de los fármacos , Receptores de Glutamato Metabotrópico/efectos de los fármacos , Análisis y Desempeño de Tareas , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos , Piperidinas/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Tiempo de Reacción/efectos de los fármacos , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/antagonistas & inhibidoresRESUMEN
BACKGROUND: A standardized neck management strategy for oral cancer patients without clinical nodal metastases remains to be established. Consequently, a decision and sensitivity analysis of two neck management protocols, involving either prophylactic neck dissection or careful observation, was conducted using the Oral Cancer Registry of Kyushu, Japan. METHODS: We calculated probabilities of subclinical nodal metastases and 5-year survival using the registry data. A two-way sensitive analysis was conducted using the probabilities and parameters of the complete nodal metastasis resection rate (x) and a utility rating that describes the health state induced by dissection (y) compared with the neck condition in a careful-observation group. RESULTS: We solved the threshold curve for y and x for the expected utility between the two groups. The results showed that prophylactic neck dissection must guarantee a complete resection of subclinical nodal metastases with no disadvantage to health state to be evaluated as equally satisfactory as careful observation. CONCLUSIONS: Careful observation involving standardized systematic preoperative and postoperative screening of the neck seems preferable to prophylactic neck dissection for oral cancer patients without subclinical nodal metastases.