Evaluation of parameters for central neuronal activity in cerebrospinal fluid of rabbits following yohimbine

Rabbits were treated intravenously with yohimbine at a dose of 5 mg/kg. The concomitant increase in noradrenergic activity was followed in function of time by measuring dopamine-beta-hydroxylase activity and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA) levels in cerebrospinal fluid. In addition, the effect of yohimbine on the dopaminergic, serotonergic and enkephalinergic neurotransmission was also determined. For this purpose, the dopamine metabolite, 3-methoxy-4-hydroxyphenylacetic acid (HVA), the serotonin metabolite, 5-hydroxy-indole acetic acid (5-HIAA) and methionine-enkephalin (Met-Enk) were quantified. The D beta H activity in control experiments, in which physiological saline was administered, increased up to 200% whereas in the yohimbine experiments a rise to 500-600% was observed. VMA and MHPG levels increased to 290%, and 209% respectively. HVA levels reached a value of 233% versus the concentration before drug injection, whereas 5-HIAA concentrations initially slightly increased and thereafter decreased. In the corresponding control experiments metabolite concentrations were virtually stable. Following yohimbine injection, methionine-enkephalin concentrations did not show significant variations compared with the control experiments. We conclude that noradrenergic and dopaminergic neurotransmission are increased following administration of the alpha 2-antagonist yohimbine whereas serotonergic neurotransmission is slightly decreased and enkephalinergic neurotransmission is unaltered. The value of the different parameters for measuring neuronal activity in cerebrospinal fluid is discussed.