RESUMO
Opioid peptides play an important role in maternal behaviour, as well as in physiological and pathological phenomena involving motivation. Daily 3.5 mg/kg doses of morphine from days 17-21 of pregnancy are able to change the expression of maternal behaviour patterns. However, the role of hormones on such opioid behavioural actions remains to be determined. The present study investigated the endocrine responses to this morphine treatment. Corticosterone, progesterone, oestradiol and prolactin serum concentrations were measured after each morphine injection. No significant differences were found in corticosterone, oestradiol or prolactin serum concentrations. The results suggest that the treatment was unable to promote different effects, other than those caused by saline injections. In morphine-treated animals, however, progesterone concentrations were consistently and significantly increased from days 18-20 of treatment. Thus, because this behavioural meaningful opioidergic stimulation during late pregnancy affects progesterone levels, the findings of the present study raise the hypothesis that this hormone may play a role in morphine-induced changes in opioid sensitivity during late pregnancy and early lactation.
Assuntos
Morfina/farmacologia , Peptídeos Opioides/farmacologia , Período Pós-Parto , Progesterona/fisiologia , Animais , Feminino , Masculino , RadioimunoensaioRESUMO
It is well established that morphine inhibits maternal behaviors. Previous studies by our group have shown activation of the rostrolateral periaqueductal gray (rlPAG) upon inhibition-intended subcutaneous injections of morphine. In this context, we demonstrated that a single naloxone infusion into the rlPAG, following this opioid-induced inhibition, reactivated maternal behaviors. Since these data were obtained by using peripheral morphine injections, the present study was designed to test whether morphine injected directly into the rlPAG would affect maternal behaviors. Our hypothesis that morphine acting through the rlPAG would disrupt maternal behaviors was confirmed with a local infusion of morphine. The mothers showed shorter latency for locomotor behavior to explore the home cage (P = 0.049). Inhibition was especially evident regarding retrieving (P = 0.002), nest building (P = 0.05) and full maternal behavior (P = 0.023). These results support the view that opioidergic transmission plays a behaviorally meaningful inhibitory role in the rostrolateral PAG.
Assuntos
Animais , Feminino , Masculino , Ratos , Comportamento Materno/efeitos dos fármacos , Morfina/farmacologia , Entorpecentes/farmacologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Animais Recém-Nascidos , Comportamento Materno/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Ratos Wistar , Tempo de Reação/efeitos dos fármacosRESUMO
It is well established that morphine inhibits maternal behaviors. Previous studies by our group have shown activation of the rostrolateral periaqueductal gray (rlPAG) upon inhibition-intended subcutaneous injections of morphine. In this context, we demonstrated that a single naloxone infusion into the rlPAG, following this opioid-induced inhibition, reactivated maternal behaviors. Since these data were obtained by using peripheral morphine injections, the present study was designed to test whether morphine injected directly into the rlPAG would affect maternal behaviors. Our hypothesis that morphine acting through the rlPAG would disrupt maternal behaviors was confirmed with a local infusion of morphine. The mothers showed shorter latency for locomotor behavior to explore the home cage (P = 0.049). Inhibition was especially evident regarding retrieving (P = 0.002), nest building (P = 0.05) and full maternal behavior (P = 0.023). These results support the view that opioidergic transmission plays a behaviorally meaningful inhibitory role in the rostrolateral PAG.
Assuntos
Comportamento Materno/efeitos dos fármacos , Morfina/farmacologia , Entorpecentes/farmacologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Feminino , Masculino , Comportamento Materno/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacosRESUMO
Opioid receptors play an important role in female physiology. They modulate directly and indirectly neuroendocrine phenomena that influence pregnancy maintenance, pain threshold, parturition, lactation, maternal behavior, rewarding and addiction. Thus understanding the gene expression levels of the three major opioid receptors, mu, delta and kappa in different brain regions is essential for investigating dynamic mechanisms of opioidergic transmission. Adult virgin female rats were treated acutely with morphine sulfate (3.5 mg/kg or 20 mg/kg s.c.) or chronically for 5 days (3.5 mg/kg). Rats were killed 1 h after the last injection. In the acute treatment, expression levels for the encoded mu-opioid receptor Oprm1, as detected by reverse transcription-polymerase chain reaction, were significantly decreased in the periaqueductal gray. In chronic treatment, both Oprk1 and Oprm1 expression levels, that encoded kappa and mu-opioid receptor respectively, showed significant decreases in the periaqueductal gray and striatum. Regional changes in opioid receptor gene expression levels might reflect highly specialized roles for these receptors with possible functional meaning for the plasticity of the opioidergic transmission.
Assuntos
Encéfalo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Morfina/administração & dosagem , Entorpecentes/farmacologia , Receptores Opioides/metabolismo , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores Opioides/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
Previous studies suggested a role for the rostral lateral periaqueductal gray (PAG) in the inhibition of maternal behavior induced by low doses of morphine in dams with previous morphine experience. In the present study, we first showed that unilateral NMDA lesions placed in this particular PAG region prevented the morphine-induced inhibition of maternal behavior in previously morphine-sensitized dams. As suggested by previous Fos data on the PAG, predatory hunting appears as a likely candidate to replace maternal behavior in the morphine-treated dams. By testing saline- and morphine-treated dams with live cockroaches only, we have presently shown that morphine challenge increased insect hunting. Moreover, morphine- and saline-treated dams were also observed in an environment containing pups and roaches. Although most of the saline-treated animals displayed active nursing and only occasionally presented insect hunting, all of the morphine-treated animals ignored the pups and avidly pursued and caught the roaches. We next questioned whether the rostral lateral PAG would be involved in this behavioral switch. Our results showed that unilateral lesions of the rostral lateral PAG, but not other parts of the PAG, partially impaired predatory hunting and restored part of the maternal response. Moreover, bilateral lesions of the rostral lateral PAG produced even more dramatic effects in inhibiting insect hunting and restoring maternal behavior. The present findings indisputably show that the rostral lateral PAG influences switching from maternal to hunting behavior in morphine-treated dams, thus supporting a previously unsuspected role for the PAG in selecting adaptive behavioral responses.