Isoquinolines,beta-carbolines and alcohol drinking: Involvement of opioid and dopaminergic mechanisms

Summary Two classes of amine-aldehyde adducts, the tetrahydroisoquinoline (TIQ) and beta-carboline (THBC) compounds, have been implicated in the mechanism in the brain underlying the addictive drinking of alcohol. One part of this review focuses on the large amount of evidence unequivocally demonstrating not only the corporeal synthesis of the TIQs and THBCs but their sequestration in brain tissue as well. Experimental studies published recently have revealed that exposure to alcohol enhances markedly the endogenous formation of condensation products. Apart from their multiple neuropharmacological actions, certain adducts when delivered directly into the brain of either the rat or monkey, to circumvent the brain's blood-barrier system, can evoke an intense and dose-dependent increase in the voluntary drinking of solutions of alcohol even in noxious concentrations. That the abnormal intake of alcohol is related functionally to opioid receptors in the brain is likely on the basis of several dinstinct lines of evidence which include: the attenuation of alcohol drinking by opioid receptor antagoists; binding of a TIQ to opiate receptors in the brain; and marked differences in enkephalin values in animals genetically predisposed to the ingestion of alcohol. Finally, it is proposed that the dopaminergic reward pathways which traverse the meso-limbic-forebrain systems of the brain more than likely constitute an integrative anatomical substrate for the adduct-opioid cascade of neuronal events which promote and sustain the aberrant drinking of alcohol.     

Human recombination hot spots hidden in regions of strong marker association

The fine-scale distribution of meiotic recombination events in the human genome can be inferred from patterns of haplotype diversity in human populations but directly studied only by high-resolution sperm typing. Both approaches indicate that crossovers are heavily clustered into narrow recombination hot spots. But our direct understanding of hot-spot properties and distributions is largely limited to sperm typing in the major histocompatibility complex (MHC). We now describe the analysis of an unremarkable 206-kb region on human chromosome 1, which identified localized regions of linkage disequilibrium breakdown that mark the locations of sperm crossover hot spots. The distribution, intensity and morphology of these hot spots are markedly similar to those in the MHC. But we also accidentally detected additional hot spots in regions of strong association. Coalescent analysis of genotype data detected most of the hot spots but showed significant differences between sperm crossover frequencies and historical recombination rates. This raises the possibility that some hot spots, particularly those in regions of strong association, may have evolved very recently and not left their full imprint on haplotype diversity. These results suggest that hot spots could be very abundant and possibly fluid features of the human genome.     

Radiation-induced leukemia in rats: Synergistic effect of urethan

Zusammenfassung Nachweis, dass i.p.-Injektion von Urethan und Ganzkörper-Röntgenbestrahlungen bei Ratten eine potenzierte leukämogene Wirkung hat, während die Zahl der entstandenen Haut- und Mamma-Tumoren geringer war als bei der Einzelbehandlung.     

Calcium evoked release of 5-hydroxytryptamine from the brain of the unanesthetized cat

Zusammenfassung Kalzium-Ionen wurden mittels lokaler Perfusion im Hypothalamus von Katzen vermehrt. Der 5-HT-Gehalt der Durchströmungsflüssigkeit nahm im Verhältnis zur Konzentration der Kalzium-Ionen zu.

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This work was supported in part by National Science Foundation Grant No. GB 7906 and US Office of Naval Research Contract No. N00014-67-A-0226-0003. We thank P.Curzon for his valuable technical assistance.     

Cerebrospinal fluid production during temperature stress and feeding in the conscious monkey

Zusammenfassung Das Flüssigkeitsvolumen des Ventrikelliquors wurde in Affen (im 3. Ventrikel kanuliert) gemessen. Die Produktion von Ventrikelliquor verringerte sich stark während 40–50 min, und zwar bei Nahrungsaufnahme, bei Erwärmung oder Abkühlung. Hernach Rückkehr des normalen Liquorvolumens.

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Supported in part by U.S. Office of Naval Research Contract No. NO 00014-67-A-0003 and Grant No. GB 7906 from the National Science Foundation. The authors are indebted to P.Curzon for valuable technical assistance.