Skip to main content
Log in

Behavioral effects of the inhibitors of phenylethanolamine-N-methyltransferase, LY 78335 and LY 134046, and their interactions with ethanol

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The centrally active inhibitors of phenylethanolamine-N-methyltransferase (PNMT), LY 78335 and LY 134046, were investigated both alone and in combination with ethanol (2 g/kg) in a holeboard test of directed exploration and locomotor activity. Both PNMT inhibitors showed dose-related reductions in exploratory head-dipping but were without effect on locomotor activity. In combination with ethanol both PNMT inhibitors tended to attenuate the ethanol-induced reductions in exploratory head-dipping but did not effect ethanol's locomotor stimulant properties. LY 134046 showed neither an anxiolytic nor an anxiogenic profile in the plusmaze test of anxiety, nor did it alter the anxiolytic effects of either 1.2 g/kg or 2 g/kg ethanol. LY 134046 did, however, attenuate the ataxic effects of a 2.4 g/kg dose of ethanol. These results may suggest a role for adrenaline synthesis in some, but not all, of the behavioral effects of ethanol.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bucher T, Redetzki H (1951) Eine photometrische Bestimmung von Athylalkohol auf ferentativem Wege. Klin Wochenschr 29:615–621

    Google Scholar 

  • Durcan MJ, Lister RG (1989) Does directed exploration influence locomotor activity in the holeboard test? Behav Neural Biol 51:121–125

    Google Scholar 

  • Durcan MJ, Lister RG, Linnoila M (1989a) Interactions of alpha2-adrenoceptor antagonists with medetomidine and with ethanol in a holeboard test. Neuropharmacology 28:275–281

    Google Scholar 

  • Durcan MJ, Lister RG, Linnoila M (1989b) Behavioral effects of alpha2-adrenoceptor antagonists and their interactions in tests of locomotion, exploration and anxiety in mice. Psychopharmacology 97:189–193

    Google Scholar 

  • File SE, Wardill AG (1975) Validity of head-dipping as a measure of exploration in a modified holeboard. Psychopharmacology 44:53–59

    Google Scholar 

  • Fuller RW (1982) Pharmacology of brain epinephrine neurons. Annu Rev Pharmacol Toxicol 22:31–55

    Google Scholar 

  • Fuller RW, Hemrick-Lueche S, Toomey RE, Horng J-S, Ruffolo RR, Molloy BB (1981) Properties of 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine, an inhibitor of norepinephrine N-methyltransferase. Biochem Pharmacol 30:1345–1352

    Google Scholar 

  • Goldstein M, Lew JY, Miyamoto T, Battista AF, Ebstein R, Hokfelt T, Fuxe K (1974) The localization and characterization of phenylethanolamine N-methyltransferase activity in specific regions of the central nervous system. Pharmacologist 16:236–243

    Google Scholar 

  • Handley SL, Mithani S (1984) Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of “fear”-motivated behavior. Naunyn-Schmiedeberg's Arch Pharmacol 327:1–5

    Google Scholar 

  • Hokfelt T, Fuxe K, Goldstein M, Johansson O (1973) Evidence for adrenaline neurons in the rat brain. Acta Physiol Scand 89:286–288

    Google Scholar 

  • Hokfelt T, Fuxe K, Goldstein M, Johansson O (1974) Immunohistochemical evidence for the existence of adrenaline neurons in the rat brain. Brain Res 66:235–251

    Google Scholar 

  • Katz RJ, Carroll BJ, Liebler L (1978) Inhibition of phenylethanolamine N-methyltransferase and brain stimulation reward. Psychopharmacology 57:39–42

    Google Scholar 

  • Lister RG (1987) The use of the plusmaze to measure anxiety in the mouse. Psychopharmacology 92:180–185

    Google Scholar 

  • Lister RG, Durcan MJ, Nutt DJ, Linnoila M (1989) Attenuation of ethanol intoxication by alpha2 adrenoceptor antagonists. Life Sci 44:111–119

    Google Scholar 

  • Majchrowicz E (1975) Induction of physical dependence upon ethanol and the associated behavioral changes. Psychopharmacology 43:245–254

    Google Scholar 

  • Mefford IN (1987) Are there epinephrine neurons in rat brain? Brain Res Rev 12:383–395

    Google Scholar 

  • Mefford IN (1988) Epinephrine in mammalian brain. Prog Neuropsychopharmacol Biol Psychiatry 12:365–388

    Google Scholar 

  • Mefford IN, Lister RG, Ota M, Linnoila M (1989) Antagonism of ethanol intoxication in rats by inhibitors of phenylethanolamine N-methyltransferase. Alcoholism: Clin Exp Res (in press)

    Google Scholar 

  • Pellow S, Chopin P, Briley M, File SE (1985) The validation of open: closed arm entries in an elevated plus-maze measure of anxiety in the rat. J Neurosci Methods 14:149–167

    Google Scholar 

  • Perry BD, Stolk JM, Vantini G, Guchait RB, U'Prichard DC (1983) Strain differences in rat brain epinephrine synthesis and alpha-adrenergic receptor number: apparent in vivo regulation of alpha-adrenergic receptors by epinephrine. Science 221:1297–1299

    Google Scholar 

  • Saavedra JM, Palkovits M, Brownstein MJ, Axelrod J (1974) Localization of phenylethanolamine N-methyl-transferase activity in specific regions of the brain. Nature 248:695–696

    Google Scholar 

  • Stolk JM, Vantini F, Perry BD, Guchait RB, U'Pritchard DC (1984) Assessment of the functional role of brain adrenergic neurons: chronic effects of phenylethanolamine N-methyltransferase inhibitors and alpha adrenergic receptor antagonists on brain norepinephrine metabolism. J Pharmacol Exp Ther 230:577–586

    Google Scholar 

  • Vantini G, Perry BD, Guchait RB, U'Pritchard DC, Stolk JM (1984) Brain epinephrine systems: detailed comparison of adrenergic and noradrenergic metabolism, receptor number and its in vitro regulation in two inbred rat strains. Brain Res 296:49–65

    Google Scholar 

  • Vogt M (1954) The concentration of sympathin in different parts of the central nervous system under normal conditions and after administration of drugs. J Physiol (Lond) 123:451–481

    Google Scholar 

  • Young WS, Kuhar MJ (1980) Noradrenergic alpha1 and alpha2 receptors: light microscopic autoradiographic localization. Proc Natl Acad Sci USA 77:1696–1700

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Durcan, M.J., Lister, R.G. & Linnoila, M. Behavioral effects of the inhibitors of phenylethanolamine-N-methyltransferase, LY 78335 and LY 134046, and their interactions with ethanol. Psychopharmacology 101, 196–202 (1990). https://doi.org/10.1007/BF02244126

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02244126

Key words

Navigation