RESUMO
Previous studies from our laboratory have shown sex differences in the behavioral, molecular, and neurochemical manifestations of morphine withdrawal and they were related to an increased sensitivity to morphine effects in males. In addition, we observed an interaction between the GABAergic and opioid systems that could also be sex-dependent. Baclofen, a GABAB receptor agonist, prevented the somatic expression and the molecular and neurochemical changes induced by morphine withdrawal syndrome in mice. On the contrary, little is known about baclofen effects in the rewarding properties of morphine in male and female mice. The present study aimed to explore the effect of baclofen (1, 2 and 3 mg/kg, i.p.) pretreatment in the rewarding effects induced by morphine (7 mg/kg, s.c.) and its effect on c-Fos and brain-derived neurotrophic factor (BDNF) expression induced by the rewarding properties of morphine in prepubertal male and female mice. Baclofen (2 mg/kg) pretreatment prevented the rewarding effects of morphine only in male mice, while baclofen (3 mg/kg) reduced these effects in both sexes. Moreover, the rewarding effects of morphine were associated with a decrease of BDNF and c-Fos expression cingulate cortex, nucleus accumbens shell, cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) areas of the hippocampus only in male mice. In addition, baclofen pretreatment prevented these changes in BDNF, but not in c-Fos expression. In conclusion, our results show that GABAB receptors have a regulatory role in the rewarding effects of morphine that could be of interest for a potential future therapeutic application in opioid use disorders.
Assuntos
Baclofeno , Fator Neurotrófico Derivado do Encéfalo , Morfina , Proteínas Proto-Oncogênicas c-fos , Recompensa , Animais , Baclofeno/farmacologia , Masculino , Feminino , Morfina/farmacologia , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Agonistas dos Receptores de GABA-B/farmacologia , Caracteres Sexuais , Comportamento Animal/efeitos dos fármacos , Fatores SexuaisRESUMO
The ability to stay alert to subtle changes in the environment and to freeze, fight or flight in the presence of predators requires integrating sensory information as well as triggering motor output to target tissues, both of which are associated with the autonomic nervous system. These reactions, which are commonly related to vertebrates, are the fundamental physiological responses that allow an animal to survive danger. The circulatory activity in vertebrates changes in opposite phases. The stage where circulatory activity is high is termed the "fight or flight stage", while the stage where circulatory activity slows down is termed the "rest and digest stage". It may be assumed that highly evolved invertebrates possess a comparable response system as they also require rapid cardiovascular and respiratory regulation to be primed when necessary. However, in invertebrates, the body plan may have developed such a system very differently. Since this topic is insufficiently studied, it is necessary to extend studies for a comparative analysis. In the present review, we use our own experimental results obtained in the crab Neohelice granulata and both older and newer findings obtained by other authors in decapod crustaceans as well as in other invertebrates, to compare the pattern of change in circulatory activity, especially in the "fight or flight" stage. We conclude that the main features of neuroautonomic regulation of the cardiac function were already present early in evolution, at least in highly evolved invertebrates, although conspicuous differences are also evident.