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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 45 (1989), S. 436-443 
    ISSN: 1420-9071
    Keywords: Alcohol ; brain ; tetrahydropapaveroline ; drinking ; opiate receptors ; dopamine ; beta-carboline ; aldehyde adducts ; tetrahydroisoquinolines ; ethanol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-6903
    Keywords: Neuropeptide-Y ; NPY ; feeding ; norepinephrine ; dopamine ; serotonin ; food intake ; HPLCCD ; satiety ; hypothalamus ; push-pull perfusion ; hunger ; paraventricular nucleus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the unrestrained rat, the hyperphagic-like ingestion of food evoked by the sustained elevation of neuropeptide-Y (NPY) in the hypothalamus was correlated with the release and turnover of monoaminergic transmitters in this structure. A single guide tube was implanted stereotaxically in the perifornical region of the hypothalamus for localized push-pull perfusion of an artificial CSF vehicle or NPY1–36 in a concentration of 10, 50, or 100 ng/1.0 μl. After the rat was fully satiated, a site reactive to NPY was perfused repeatedly at a rate of 20 μl/min for 6.0 min with an interval of 6.0–12 min elapsing between each perfusion. Samples of perfusate were analyzed by HPLC with coulometric detection for DA, HVA, DOPAC, NE, MHPG, 5-HT, and 5-HIAA. Although control perfusions were without effect on feeding or monoamine activity, NPY evoked mean cumulative intakes of food of 14±2.4, 25.6±3.0 and 26.5±3.2 g in response to 10, 50, or 100 ng/μl concentrations of NPY, respectively, over the 4.0–5.0 hr test interval. HPLC analyses showed that during feeding the release of both NE and DA was enhanced significantly. The turnover of both catecholamines likewise increased significantly as reflected by the elevated levels of MHPG, DOPAC and HVA. However, neither the basal efflux of 5-HT nor its turnover, as reflected by the output of 5-HIAA, was affected during feeding induced by NPY perfused in the hypothalamus. These results suggest that a sustained elevation of NPY in the hypothalamus causes a perturbation in the basal activity of NE and DA which are both implicated in the neuronal mechanism regulating normal eating behavior. Thus, these catecholamine neurotransmitters are envisaged to comprise an intermediary step in the functional role played by NPY in the hypothalamus in integrating the control of energy metabolism and caloric intake.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-6903
    Keywords: Harman ; 1-methyl-β-Carboline ; osmotic minipump ; hippocampus serotonin ; norepinephrine ; dopamine ; aldehyde metabolites ; alcohol drinking ; ethanol ; brain regions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Harman (1-methyl-β-carboline) has been shown to induce preference for alcohol in the genetically bred, low alcohol drinking (LAD) rat. This study was undertaken in the LAD rat to determine whether monoamines and their metabolites in different regions of the brain are altered by harman infused chronically into the dorsal hippocampus. For this purpose, a cannula was implanted stereotaxically into the dorsal hippocampus. The cannula was attached to an osmotic minipump implanted subcutaneously within the intrascapular space. The pump was filled with either an artificial cerebrospinal fluid (CSF) vehicle or harman, which was delivered at a rate of 1.0 or 3.0 μg/h (i.e., 5.5 or 16.5 nmol/h, respectively) for a period of 14 days. Four days after surgery, a standard preference test for ethyl alcohol was given to the rats over 10 days in which concentrations were increased daily from 3%–30%. The higher concentration of harman infused into the hippocampus elevated the level of serotonin (5-HT), both ipsilateral and contralateral to the hippocampal site of infusion, as well as in the midbrain, frontal cortex, striatum and nucleus accumbens. Similarly, this treatment resulted in a rise in the levels of norepinephrine in the hippocampus and midbrain but aecreases in dopamine levels in the pons. The levels of 5-hydroxyindoleacetic acid (5-HIAA) and: 3,4-dihydroxyphenylacetic acid (DOPAC) were diminished in the pons of rats given 3.0 μg/h harman, whereas both concentrations of the β-carboline reduced the level of homovanillic acid (HVA) in the frontal cortex. These harman-induced changes in the metabolism of the amines are possibly the result of an inhibition of monoamine oxidase (MAO). When the harman-induced shifts in the neurochemical values were compared to the alcohol intakes of the rats as reported previously, no significant correlation was found. The absence of this concordance suggests that the alterations in the monoamine neurotransmitters produced by harman and the voluntary intake of alcohol induced by this β-carboline may not originate from the same systems in the brain.
    Type of Medium: Electronic Resource
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