δ9-Tetrahydrocannabinol affects mesolimbic dopaminergic activity in the female rat brain: interactions with estrogens

Summary In this work, we studied the possible estrogenic modulation of the effects of ⁹-tetrahydrocannabinol (THC) on mesolimbic dopaminergic activity, by examining the effects of an acute dose of this cannabinoid: (i) during the estrous cycle; (ii) after ovariectomy, chronic estrogen-replacement and tamoxifen (TMX)-induced blockade of estrogenic receptors; and (iii) combined with a single and physiological injection of estradiol to ovariectomized rats. THC significantly decreased the density of D1 dopaminergic receptors and non-significantly increased the L-3,4-dihydroxyphenylacetic acid (DOPAC) content in the limbic forebrain of ovariectomized rats chronically replaced with estrogens. The decrease in D1 receptors was also produced by TMX, whereas the coadministration of both THC and TMX did not lead to a major decrease. In addition to the trend of THC increasing DOPAC content, this cannabinoid was also able to increase the ratio between DOPAC and dopamine, although this last effect only occurred after coadministration of THC and TMX, which had been ineffective administered individually. All these effects were not seen when THC was administered to normal cycling rats during each phase of estrous cycle and to ovariectomized rats without chronic estrogen replacement or only submitted to a single and acute dose of estradiol. This observation might be related to the fact that the density of limbic cannabinoid receptors increased in chronic estrogen-replaced ovariectomized ratsversus normal cycling, ovariectomized or acutely estrogen-treated ovariectomized rats. Interestingly, THC administration in ovariectomized rats was followed by a slight, although significant, increase in tyrosine hydroxylase activity, which was also observed after coadministration of THC with a short-time and acute dose of estradiol. In summary, THC stimulated the presynaptic activity of mesolimbic dopaminergic neurons, but accompanied by a decrease in their postsynaptic sensitivity. These effects did not appear in normal cycling rats being only evident after ovariectomy and chronic estrogen replacement, which might be related to changes in binding characteristics of cannabinoid receptors in this area. Moreover, some of them appeared after TMX-induced blockade of estrogenic cytosolic receptors, which likely suggests the existence of a certain estrogenic modulation of the actions of THC on mesolimbic neurons. On the contrary, coadministration of THC with a single and shortly tested dose of estradiol was always ineffective in modifying THC effects.Presented in abstract form to the Third IBRO World Congress of Neuroscience, Montreal (Canada), August 4–9, 1991     

Effect of prenatal and postnatal exposure to therapeutic doses of chlorimipramine on emotionality in the rat

Prenatal administration of high doses of tricyclic antidepressants have been reported to produce teratogenic and behavioral effects in rat offspring. In the present work, behavioral abnormalities are described in offspring of rats treated with therapeutic doses of chlorimipramine (CIM) during pregnancy (CIM-P), lactation (CIM-L) and during the whole pregnancy-lactation period (CIM-PL). CIM-P treatment did not produce teratogenic effects, did not affect number or body weight of pups at birth and did not induce neonatal mortality. At 2 months of age, the CIM-P males showed a significant increase in digging and grooming (familiar environment test), a decrease in exploration (novel environment test) and a decrease in active social interactions (social behavior test). Females were more resistant than males to the prenatal CIM treatment. The results suggest increased emotionality in CIM-P pups. Some behavioral abnormalities were also observed in the tests performed at 4 months of age. CIM-L treatment had minor effects on litter behavior. CIM-PL treatment potentiated the effects of the CIM-P treatment. In the CIM-PL males, impairment of exploration of a novel environment still remained in the tests performed at 4 months of age. It is speculated that when prenatal brain development is altered by CIM, further postnatal treatment may impair compensatory processes occurring in early postnatal life.     

bFGF stimulates GAP-43 phosphorylation at ser41 and modifies its intracellular localization in cultured hippocampal neurons

Cultured hippocampal neurons have been used to study GAP-43 phosphorylation and subcellular distribution. By immunofluorescence, GAP-43 was found associated with adherent membrane patches that remained attached to the substratum after in situ permeabilization with Nonidet-NP40. This association increases during neuronal development and is stabilized by the actin cytoskeleton. Basic fibroblast growth factor (bFGF) promotes GAP-43 translocation from the cytosol to adherent membrane patches and, at the same time, stimulates GAP-43 phosphorylation, mainly at the protein kinase C (PKC) site (Ser41). Inhibition of PKC prevented bFGF-stimulated GAP-43 phosphorylation and translocation, while activation by phorbol esters mimicked bFGF effects, suggesting that phosphorylation at Ser41 regulates GAP-43 subcellular localization. Using biochemical fractionation and phosphorylation analysis, it was found that Ser41 phosphorylation was highest in cytoskeleton-associated GAP-43 and lowest in membrane-associated GAP-43. It is proposed that GAP-43 is continuously cycling between intracellular compartments depending on its phosphorylation state and could be taking part in initial adhesive complexes assembled during growth cone advance.     

MAO-A and MAO-B localisation in human lung and spleen

Localisation of MAO-A and -B in human lung and spleen was studied by immunohistochemistry. The primary antibodies used were mouse monoclonal anti-human MAO-A (6G11/E1) and anti-human MAO-B (3F12/G10/2E3). Samples of lung and spleen were obtained from 6 routine autopsy cases. Both immunoreactivities showed a homogeneous distribution in lung, where all cell types had both MAO-A and -B staining. In spleen MAO-A and -B showed a very weak immunoreactivity, which was restricted to smooth muscle cells and reticular cells of the white pulp. These data represent the most comprehensive study of MAO-A and -B localisation in the two tissues.     

Retroperitoneal benign schwannoma. Report of a new case

The schwannoma is a tumor resulting from the Schwann cells of neural shwath, being its retroperitoneal localization quite unusual. This tumor is clinically unspecified and in most of the cases it originates symptoms coming from the compression of the close structures when its localization is retroperitoneal. Its diagnosis is quite often fortuitous being confirmed by anatomopathological study afterwards. The treatment is surgical radical exeresis with subsequent followup. We report a new case of this uncommon retroperitoneal pathology in a female patient showing a nonspecific clinic. Two years after the surgery she remains asymptomatic without any radiological evidence of recidive.     

Congenital bladder diverticulum and Ehlers-Danlos syndrome: an unusual association

The existence of a vesical diverticulum in the context of a congenital connective tissue disorder such as Ehlers-Danlos syndrome led us to consider the possibility of a relationship. Four types of diverticula can be found in the literature: congenital, acquired, iatrogenic and syndrome-associated. Within the later, Ehlers-Danlos syndromes type IV and IX, even type V, are associated to the existence of vesical diverticula. The potential spontaneous rupture of the diverticulum is a typical feature, as well as post-surgery relapse. The attitude towards such diverticula should be one of watchful waiting, and simple, plasty-free diverticulectomy on the bladder's neck is indicated when performing a surgical procedure.     

Technical solution in kidney retransplantation in a patient with femoro-femoral bypass

Over the last decade kidney transplantation has become a common therapeutic procedure for patients with end-stage renal diseases. Between 1988 and 1998 donors rate per million population has dramatically increased in our environment, thus providing us with more chances to offer kidney transplantation to a larger number of patients. The technico-surgical difficulties that have to be faced however, are increasingly frequent and require a search for new approaches and innovative changes to the usual surgical techniques for our patient's benefit.