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The purpose of this study was to investigate the effects of the endogenous cannabinoid arachidonoyl-ethanolamide, anandamide (AEA), on the activity of the hypothalamo-pituitary-adrenal (HPA) axis in cannabinoid receptor (CB[sub 1] receptor) inactivated (KO) mice. A low dose (0.01 mg/kg i.p.) of AEA significantly increased plasma corticotropin (ACTH) and corticosterone concentrations in both wild-type (+/+) and in mutant (–/–) animals. In each case, hormone levels reached their peaks at 90 min after AEA administration. In a parallel experiment, AEA administration was preceded by the injection of SR 141716A (1.0 mg/kg), a selective and potent CB[sub 1] receptor antagonist, or of capsazepine (5.0 mg/kg), a potent vanilloid receptor of type 1 (VR1) antagonist. The latter drugs did not prevent the effects of AEA on the HPA axis. Using Fos protein immunohistochemistry, we observed that the parvocellular part of the hypothalamic paraventricular nucleus (PVN) was activated as early as 45 min after AEA injection and reached peak levels after 60 min in both +/+ and –/– mice. Furthermore, the CB[sub 1] and VR1 receptor antagonists did not block the effects of AEA on Fos immunoreactivity. The results strongly support the view that activation of the HPA axis produced by AEA possibly occurs via a currently unknown (CB[sub x] ) cannabinoid receptor present in PVN. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Several data suggest that the endogenous cannabinoid system plays a role in neuroendocrine regulation in adult individuals, although the information on its involvement in peri-pubertal processes is scarce. In the present study, we have examined the ontogeny (from postnatal day [PND] 5 up to adulthood) of hypothalamic and anterior pituitary contents of anandamide (arachidonyl-ethanolamide, AEA). We observed that the content of AEA in the hypothalamus was low at PND5, PND15 and PND25, but it markedly increased (approximately 3-fold) immediately before the puberty (on the day of 1st proestrus), to return to intermediate values immediately after the vaginal opening (day of 2nd proestrus) and, eventually, adulthood. By contrast, no consistent differences were observed in AEA levels in the anterior pituitary. These results demonstrate the occurrence of a parallelism between the peri-pubertal events and a rise in the hypothalamic content of AEA immediately before the puberty, which might indicate that this endocannabinoid may be involved in the onset of puberty in rats. [Copyright &y& Elsevier]

Most data on effects of natural and synthetic cannabinoids on anterior pituitary hormone secretion point out to a primary impact on the hypothalamus. There is also some evidence, however, of possible direct actions of these compounds on the anterior pituitary, although the presence of cannabinoid receptors in the pituitary has not been documented as yet. In the present study, we evaluated the presence of cannabinoid CB[sub 1] receptor-mRNA transcripts in the pituitary gland by in situ hybridization. We observed CB[sub 1] receptor-mRNA transcripts in the anterior pituitary and to a lesser extent in the intermediate lobe whereas they were absent in the neural lobe. We then examined whether CB[sub 1] receptor-mRNA levels in both pituitary lobes responded to chronic activation by a specific agonist, as did receptors located in adjacent hypothalamic nuclei and in other brain regions. Daily administration of CP-55,940 for 18 days produced a small, but statistically significant paradoxical increase in CB[sub 1] receptor-mRNA levels in the anterior pituitary, with no changes in the intermediate lobe, in contrast to reduced CB[sub 1] receptor-mRNA levels observed in the ventromedial hypothalamic nucleus (VMN), and to decreased CB[sub 1] receptor binding in the VMN and the arcuate nucleus. The time-course of up-regulation of CB[sub 1] receptor-mRNA transcripts in the anterior lobe was biphasic; daily administration of Δ[sup 9] -tetrahydrocannabinol produced an early and marked decrease in CB[sub 1] receptor-mRNA levels after 1 and 3 days, followed by normalization after 7 days and by a small increase after 14 days. We also checked whether endogenous cannabinoid ligands are present in the anterior pituitary and the hypothalamus. Although anandamide itself was detected only in trace amounts, concentrations of its precursor N-arachidonoyl-phosphatidyl-ethanolamine and of 2-arachidonoyl-glycerol were found in both tissues, suggesting that endocannabinoids may be synthetized in the anterior pituitary. In summary, CB[sub 1] receptors and corresponding ligands seem to be expressed in cells of the anterior and intermediate lobes of the pituitary, but the response of CB[sub 1] receptor-mRNA transcripts in the anterior lobe to chronic agonist activation is different than the desensitization observed in hypothalamic nuclei. [ABSTRACT FROM AUTHOR]

Abstract: The effect of endocannabinoids on synaptic plasticity has been demonstrated in a variety of species and brain regions. Relatively little is known about the localization and significance of cannabinoid (CB) receptors in the avian brain. The objective of the present study was to investigate the effect of a specific CB1 receptor antagonist upon the acquisition and consolidation of memory in young domestic chicks. One-day-old domestic chicks (Gallus domesticus) were trained and tested by the passive avoidance paradigm. Systemic (i.p.) administration of the CB1 receptor antagonist rimonabant in a dose of 1mg/kg 30min before the training failed to affect learning, but a similar treatment 30min before the recall (5.5h after training) attenuated the retention in 60% of animals. In another set of animals, a dose of 0.01mg/kg produced no significant impairment, whereas doses 0.1mg/kg and 1.0mg/kg resulted in significant attenuation in passive avoidance performance when tested 30min prior to recall. The results are discussed in terms of a putative mediating role of CB receptors in the consolidation of memory. [Copyright &y& Elsevier]

CB1 receptor agonists inhibit stimulated gastric acid secretion and exert an anti-ulcer activity in acid-dependent ulcer models. The aims of this study were to investigate the gastroprotective effect of cannabinoids in an acid-independent ulcer model and to analyze the role of opioid and vanilloid receptors in this effect. Gastric mucosal damage was induced by acidified ethanol in rats and in CB1+/+ and CB1-/- mice. Anandamide, methanandamide and WIN-55,212-2 inhibited the ethanol-induced gastric mucosal damage significantly after peripheral and central administration, and their effects were reversed by the CB1 receptor antagonist SR141716A. The gastroprotective effect of cannabinoid agonists was significantly decreased by naloxone and partially by capsazepine (TPRV1 receptor antagonist). The gastroprotective effect of opioid peptides DAGO and deltorphin II was significantly reduced in CB1-/- mice. In conclusion, cannabinoid CB1 receptors are likely to be involved in gastric mucosal defense. The effect seems to be central, and correlation between opioid and cannabinoid system in gastric mucosal protection may be raised. [ABSTRACT FROM AUTHOR]

Abstract: Formerly considered as an exclusively peripheral receptor, it is now accepted that CB2 cannabinoid receptor is also present in limited amounts and distinct locations in the brain of several animal species, including mice. However, the possible roles of CB2 receptors in the brain need to be clarified. The aim of our work was to study the μ-opioid receptor (MOR) mRNA expression level and functional activity after acute in vivo and in vitro treatments with the endocannabinoid noladin ether (NE) and with the CB2 receptor antagonist SR144528 in brainstem of mice deficient in either CB1 or CB2 receptors. This study is based on our previous observations that noladin ether (NE) produces decrease in the activity of MOR in forebrain and this attenuation can be antagonized by the CB2 cannabinoid antagonist SR144528, suggesting a CB2 receptor mediated effect. We used quantitative real-time PCR to examine the changes of MOR mRNA levels, [35S]GTPγS binding assay to analyze the capability of μ-opioid agonist DAMGO to activate G-proteins and competition binding assays to directly measure the ligand binding to MOR in mice brainstem. After acute NE administration no significant changes were observed on MOR signaling. Nevertheless pretreatment of mice with SR144528 prior to the administration of NE significantly decreased MOR signaling suggesting the involvement of SR144528 in mediating the effect of MOR. mRNA expression of MORs significantly decreased both in CB1 wild-type and CB1 knockout mice after a single injection of SR144528 at 0.1mg/kg when compared to the vehicle treated controls. Consequently, MOR-mediated signaling was attenuated after acute in vivo treatment with SR144528 in both CB1 wild-type and CB1 knockout mice. In vitro addition of 1μM SR144528 caused a decrease in the maximal stimulation of DAMGO in [35S]GTPγS binding assays in CB2 wild-type brainstem membranes whereas no significant changes were observed in CB2 receptor knockouts. Radioligand binding competition studies showed that the noticed effect of SR144528 on MOR signaling is not mediated through MORs. Our data demonstrate that the SR144528 caused pronounced decrease in the activity of MOR is mediated via CB2 cannabinoid receptors. [Copyright &y& Elsevier]

It has been shown that the endocannabinoids inhibit luteinizing hormone (LH) and prolactin (PRL) secretion. When the effects of the two well-known endocannabinoids arachidonoylethanolamide (AEA, anandamide) and 2-arachidonoyl-glycerol (2AG) have been compared it became evident that AEA caused inhibition was higher than that one of 2AG. AEA also diminished the two investigated hormonal levels in CB1 receptor inactivated mice. AEA, being an endogenous ligand of vanilloid type 1 (TPRV1) receptor, while activating TPRV1 receptor has an effect on both LH and PRL levels decrease because these later were abolished when capsazepin, antagonist of TPRV1 receptor was previously administered to the CB1 KO animals. We postulate that the difference between the effects of AEA and 2AG on the serum levels of LH and PRL is due to the difference in receptor activation of these two compounds, namely AEA can activate both CB1 and TRPV1 receptor but 2AG acts only on CB1 receptor.

The peptide guanylin, first isolated from rat small intestine, is involved in the regulation of water-electrolyte transport between the intracellular and extracellular compartments of the epithelia. The main sites of guanylin expression are the intestinal, airway, or exocrine gland ductal epithelia where guanylin acts in a paracrine/luminocrine fashion. Because guanylin also circulates in the blood, sources of this peptide were sought in endocrine glands. Our group has already demonstrated the presence of guanylin-immunoreactive cells in the pars tuberalis of male rat adenohypophysis. In this study, we investigated whether guanylin-immunoreactive cells exist also in the adenohypophysial pars distalis and whether their appearance or distribution correlates with various physiological conditions in female rats or alters after gonadectomy in both sexes. These studies revealed that the rat pars distalis contains two guanylin-immunoreactive cell types, gonadotrophic cells, whose number varied notably during the estrous cycle, reached a peak in the proestrous phase, and increased consistently during pregnancy, in lactating animals, and after gonadectomy, and folliculo-stellate cells, a discrete number of which were found only in female rats at the estrous phase. These findings suggest that guanylin is involved in regulating gonadotrophic cell function. They also add important information on the controversially discussed functions of folliculo-stellate cells.

Central cannabinoid receptors (CB1 receptors) are densely located in the output nuclei of the basal ganglia (globus pallidus, substantia nigra pars reticulata). Endogenous cannabinoids appear to modulate transmitter systems (e.g. dopamine) within the basal ganglia. In the striatum, CB1 receptors are localized on the same neurons as Gi-coupled dopamine D2 receptors. Striatal CB1 receptors are also negatively linked to adenylcyase, and may modulate dopamine release. The presence of CB1 receptors in dopaminergic neurons strongly suggests that cannabinoids play a modulatory role in dopaminergic neuronal pathways. This co-localization may postulate "cross talk" between endocannabinoids and dopamine-dependent reward mechanisms.