A combined microdialysis/microinfusion technique was used to investigate whether arginine vasopressin (AVP) is involved in the regulation of its own release into the extracellular fluid of the ...supraoptic nucleus in vivo. While intranuclear neuropeptide release was monitored, 0.33 microliter of either vehicle, lysine vasopressin (LVP; 10 ng microliters -1) or a V1/V2 AVP receptor antagonist (100 ng microliters -1) was infused into the supraoptic nucleus of adult male Wistar rats before and during direct osmotic stimulation of the nucleus via the microdialysis probe. Administration of LVP increased basal AVP release, whereas administration of the V1/V2 receptor antagonist attenuated the increase in AVP release during osmotic stimulation observed in vehicle-treated controls. Taken together, these results indicate a receptor-mediated positive feedback action of endogenous AVP on its own release within the supraoptic nucleus.
OBJETIVO: Este artigo revisa o sistema endocanabinoide e as respectivas estratégias de intervenções farmacológicas. MÉTODO: Realizou-se uma revisão da literatura sobre o sistema endocanabinoide e a ...sua farmacologia, considerando-se artigos originais ou de revisão escritos em inglês. DISCUSSÃO: Canabinoides são um grupo de compostos presentes na Cannabis Sativa (maconha), a exemplo do Δ9-tetraidrocanabinol e seus análogos sintéticos. Estudos sobre o seu perfil farmacológico levaram à descoberta do sistema endocanabinoide do cérebro de mamíferos. Este sistema é composto por pelo menos dois receptores acoplados a uma proteína G, CB1 e CB2, pelos seus ligantes endógenos (endocanabinoides; a exemplo da anandamida e do 2-araquidonoil glicerol) e pelas enzimas responsáveis por sintetizá-los e metabolizá-los. Os endocanabinoides representam uma classe de mensageiros neurais que são sintetizados sob demanda e liberados de neurônios pós-sinápticos para restringir a liberação de neurotransmissores clássicos de terminais pré-sinápticos. Esta sinalização retrógrada modula uma diversidade de funções cerebrais, incluindo ansiedade, medo e humor, em que a ativação de receptores CB1 pode exercer efeitos dos tipos ansiolítico e antidepressivo em estudos préclínicos. CONCLUSÃO: Experimentos com modelos animais sugerem que drogas que facilitam a ação dos endocanabinoides podem representar uma nova estratégia para o tratamento de transtornos de ansiedade e depressão.OBJECTIVE: The present review provides a brief introduction into the endocannabinoid system and discusses main strategies of pharmacological interventions. METHOD: We have reviewed the literature relating to the endocannabinoid system and its pharmacology; both original and review articles written in English were considered. DISCUSSION: Cannabinoids are a group of compounds present in Cannabis Sativa (hemp), such as Δ9-tetrahydrocannabinol, and their synthetic analogues. Research on their pharmacological profile led to the discovery of the endocannabinoid system in the mammalian brain. This system comprises at least two G-protein coupled receptors, CB1 and CB2, their endogenous ligands (endocannabinoids; e.g. the fatty acid derivatives anandamide and 2-arachydonoyl glycerol), and the enzymes responsible for endocannabinoid synthesis and catabolism. Endocannabinoids represent a class of neuromessengers, which are synthesized on demand and released from post-synaptic neurons to restrain the release of classical neurotransmitters from pre-synaptic terminals.This retrograde signalling modulates a variety of brain functions, including anxiety, fear and mood, whereby activation of CB1 receptors was shown to exert anxiolytic-and antidepressant-like effects in preclinical studies. CONCLUSION: Animal experiments suggest that drugs promoting endocannabinoid action may represent a novel strategy for the treatment of depression and anxiety disorders.
Spatial navigation is a fundamental capability necessary in everyday life to locate food, social partners and shelter. It results from two very different strategies: (i) place learning which enables ...for flexible way finding and (ii) response learning that leads to a more rigid ‘route following’. Despite the importance of knockout techniques that are only available in mice, little is known about mice’ flexibility in spatial navigation tasks.Here we demonstrate for C57BL6/N mice in a water-cross maze that only place learning enables spatial flexibility and relearning of a platform position, whereas response learning does not. This capability depends on an intact hippocampal formation, since hippocampus lesions by ibotenic acid disrupted relearning. In vivo manganese-enhanced magnetic resonance imaging revealed a volume loss of ≥ 60% of the hippocampus as a critical threshold for relearning impairments. In particular the changes in the left ventral hippocampus were indicative of relearning deficits.In summary, our findings establish the importance of hippocampus-dependent place learning for spatial flexibility and provide a first systematic analysis on spatial flexibility in mice.
This study examined the effects of direct osmotic stimulation of the hypothalamic paraventricular nucleus (PVN) on grooming behavior of adult male rats. Animals chronically fitted with a ...microdialysis probe in the right PVN responded to dialysis with hypertonic (containing 1 M NaCl) artificial cerebrospinal fluid (aCSF) with grooming behavior (to approx. 500%, P < 0.01, ANOVA) and a significantly reduced time resting (to approx. 20%, P < 0.01, ANOVA), compared with controls which received either the same treatment in the right supraoptic nucleus or in which the PVN was dialyzed with isotonic (0.15 M NaCl) a CSF. These results indicate that direct osmotic stimulation of the PVN via microdialysis is able to trigger and to maintain excessive grooming activity in rats; the novel experimental approach used here provides the potential to investigate the involvement of endogenous, intracerebrally released substances in the grooming response.
We studied the role of central amygdala CRH receptors in behavioral responses to an anxiogenic stimulus. An antisense oligodeoxynucleotide corresponding to the rat CRH
1 receptor mRNA was infused ...chronically into the central amygdaloid nucleus of male rats via osmotic minipumps (0.25 μg/0.5 μl/h). Control groups received infusions of either a scrambled sequence oligodeoxynucleotide or vehicle. On the 4th day of treatment, rats were subjected to 10 min of social defeat and immediately afterwards tested on the elevated plus-maze. Antisense oligodeoxynucleotide-treated rats spent significantly more time exploring the open arms of the plus-maze than scrambled sequence- and vehicle-treated animals, both of which did not differ from each other. The social discrimination test, on the other hand, revealed no difference in juvenile recognition abilities among the treatment groups. Using in situ hybridization and receptor autoradiography, we were not able to detect clear signals of CRH
1 receptor mRNA and CRH binding sites in the central amygdaloid nucleus of either group, confirming the reportedly low expression and density of CRH receptors in this brain area. The present data support the view that CRH receptors in the central nucleus of the amygdala are involved in the mediation and expression of anxiety-related behavior, but simultaneously raise questions as to the mechanisms of antisense oligodeoxynucleotide action.
PDF
