Mice were rendered barbiturate-dependent by chronic feeding with barbital-con taining food. Brain dopamine turnover was significantly increased in barbital withdrawal, whereas 5-hydroxytryptamine (5-HT) turnover was significantly decreased. Severity of with drawal was assessed by measuring the convulsions following a dose of 33 mg/kg mer captopropionate (MPA). The neurotoxins 6-hydroxydopamine and 5,6-dihydroxytryptamine as well as metergoline (5 mg/kg) increased the severity of MPA convulsions. Quipazine (20 mg/ kg) attenuated the convulsions. The results are consistent with the hypothesis that diminished 5-HT function may contribute to the barbital withdrawal syndrome. Behavioural responses to serotonergic drugs were enhanced in barbital-dependent mice compared to controls, but [3H]- 5-HT binding to crude membrane fractions was similar in both groups with a single high affinity site.
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References
1.
Anisman H.1977Neurochemical changes elicited by stress. Behavioural correlates In Psychopharmacology of aversely motivated behaviour. H Anisman, G Bignami eds. Plenum Press, New York, pp. 119-172
2.
Barlow R.B.1983Biodata handling with microcomputersElsevier Biosoft, Cambridge, England
3.
Bennett J.P., Snyder S.H.1976Serotonin and lysergic acid diethylamide binding in rat brain membranes: relationship to postsynaptic serotonin receptorsMolecular Pharmacology12: 373-389
4.
Bowery N.G., Hill D.R., Hudson A.L., Doble A., Middlemiss D.N., Shaw J., Turnbull M.1980 (-)-Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptorNature 283: 92-94
5.
Brittain R.T., Handley S.L.1967Temperature changes produced by the injection of catecholamines and 5-hydroxytryptamine into the cerebral ventricles of the conscious mouseJournal of Physiology (London) 192: 805-813
6.
Collinge J., Pycock C.J., Taberner P.V.1983Studies on the interaction between cerebral 5-hydroxytryptamine and γ-aminobutyric acid in the mode of action of diazepam in the ratBritish Journal of Pharmacology79: 637-643
7.
Corrodi H., Fuxe K., and Hokfelt T.1966The effects of barbiturates on the activity of the catecholamine neurons in rat brainJournal of Pharmacy and Pharmacology18: 556-558
8.
Crossland J., Leonard B.E.1963Barbiturate withdrawal convulsions in the ratBiochemical Pharmacology12(suppl), 103
9.
Curzon G.1981The turnover of 5-hydroxytryptamine. In Central neurotransmitter turnover C J Pycock, P V Taberner eds. Croom Helm, London, pp. 59-80
10.
Forchetti C.M., Meek J.L.1981Evidence for a tonic GABAergic control of serotonin neurones in the median raphe nucleusBrain Research26: 208-212
11.
Frankel D., Khanna J.M., LeBlanc A.E., Kalant H.1975Effect of p-CPA on the acquisition of tolerance to ethanol and pentobarbitalPsychopharmacologia44: 247-252
12.
Grahame-Smith D.G.1971Studies in vivo on the relationship between brain tryptophan, brain 5-HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and 1-tryptophanJournal of Neurochemistry18: 1053-1066
13.
Gray J.A., Metz A., Goodwin G.M., Green A.R.1986The effects of the GABA-mimetic drugs progabide and baclofen on the biochemistry and function of 5-hydroxytryptamine and noradrenalineNeuropharmacology25: 711-716
14.
Gray P.L., Taberner P.V.1985Evidence for GABA tolerance in barbiturate-dependent and withdrawn miceNeuropharmacology24: 437-444
15.
Gray P.L., Taberner P.V.1986Alterations in 5-HT function during barbiturate dependence and withdrawal in miceBritish Journal of Addiction81: 709
16.
Ho I.K., Harris R.A.1981Mechanism of action of barbituratesAnnual Review of Pharmacology and Toxicology21: 83-111
17.
Lamar C.1970Mercaptopropionic acid; a convulsant that inhibits glutamate decarboxylaseJournal of Neurochemistry17: 165-170
18.
Lidbrink P., Corrodi H., Fuxe K., Olson L.1972Barbiturates and meprobamate: decreases in catecholamine turnover of central dopamine and noradrenaline neuronal systems and the influence of immobilization stressBrain Research45: 507-524
19.
Lidbrink P., Corrodi H., Fuxe K.1974Benzodiazepines and barbiturates: turnover changes in central 5-hydroxytryptamine pathwaysEuropean Journal of Pharmacology26. 35-40
20.
Lyness W.H., Mycek M.J.1980The role of cerebral serotonin in the development of tolerance to phenobarbitalBrain Research 187: 443-456
21.
Mefford I.N.1981Application of high performance liquid chromatography with electrochemical detection to neurochemical analysis: measurement of catecholamines, serotonin, and metabolites in rat brainJournal of Neuroscience Methods3: 207-224
22.
Morgan W.W.1976Effect of 6-hydroxydopamine pretreatment on spontaneous convulsions induced by barbital withdrawalExperientia32: 489-491
23.
Morgan W.W., Huffman R.D., Pfeil K.A., Gonzales E.G.1978Effects of synthesis inhibition on the levels of brain catecholamines in barbital-dependent ratsPsychopharmacology46: 41-44
24.
Nabeshima T., Ho I.K.1981Acute and chronic effects of pentobarbital on 5-hydroxytryptamine in mouse brainProgress in Neuropsychopharmacology5: 121-128
25.
Nelson, O.L., Herbert A., Bourgoin S., Glowinski J., Hamon M.1978Characteristics of central 5-HT receptors and their adaptive changes following intracerebral 5,7-dihydroxytryptamine administration in the rat. Molecular Pharmacology14: 983-995
26.
Sharman D.F.1981The turnover of catecholamines In Central neurotransmitter turnover C J Pycock, P V Taberner eds. Croom Helm, London, pp. 20-58
27.
Trulson M.E., Jacobs B.L.1976Behavioural evidence for rapid release of CNS serotonin by PCA and fenfluramineEuropean Journal of Pharmacology36: 149-154
Westfall T.C., Tittermary V.1982Inhibition of the electrically induced release of [ 3H]-dopamine by serotonin from super-fused rat striatal slicesNeuroscience Letters28: 205-209
