A behavioural and neurochemical analysis of chronic and selective monoamine oxidase inhibition

Psychopharmacology (Berl). 1987;92(1):42-7. doi: 10.1007/BF00215477.

Abstract

The effects of clorgyline were compared with the effects of (-)-deprenyl using measures of rewarding hypothalamic self-stimulation, regional monoamine metabolism and monoamine oxidase activity. Male Wistar rats trained to self-stimulate at half-maximal rates with unilateral bipolar lateral hypothalamic electrodes on a continuous reinforcement schedule were implanted subcutaneously with osmotic minipumps which delivered 1 mg X kg-1 drug per day or vehicle for 13 days. A response rate/stimulation frequency (reward summation) function was determined the day before minipump implantation and on days 5 and 13 of drug administration. Only clorgyline induced a shift to the left in the reward summation function at 5 and 13 days, indicating enhancement of reinforcement. Clonidine (50 micrograms X kg-1 IP) probe tests were run on days 2 and 10 to determine the sensitivity of alpha 2-noradrenaline receptors. Clorgyline induced an attenuation of the clonidine response on day 10 relative to day 2. The other groups exhibited no change in response to clonidine. Clorgyline also induced a progressive increase in self-stimulation rates; this effect was not observed with the other groups. The clorgyline effects were accompanied by an increase in regional brain levels of dopamine, noradrenaline and 5-hydroxytryptamine and a reduction of their acid metabolites. Clorgyline selectively inhibited type A monoamine oxidase, whereas (-)-deprenyl selectively inhibited type B monoamine oxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain Chemistry / drug effects*
  • Clonidine / pharmacology
  • Male
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Selegiline / pharmacology
  • Self Stimulation

Substances

  • Monoamine Oxidase Inhibitors
  • Selegiline
  • Clonidine