The yohimbine-induced anticonflict effect in the rat, Part II. Neurochemical findings.

Abstract

In a companion paper the alpha 2-adrenoceptor antagonist yohimbine was found to produce a dose-dependent anticonflict effect in a modified Vogel's conflict test. The behavioral data further indicated that noradrenergic and serotonergic neurons as well as the benzodiazepine (BDZ) receptor may be involved in the anticonflict effect of yohimbine. In the present study the effects on rat brain monoamine neurochemistry and GABAA/BDZ receptor function (36Cl-uptake in corticohippocampal synaptoneurosomes) of a maximally anticonflict producing dose of yohimbine (4.0 mg/kg, i.p.) were studied. The levels of rat brain catecholamines and indoleamines were measured ex vivo using high performance liquid chromatography with electrochemical detection (HPLC-ED). Yohimbine decreased noradrenaline levels both in the hippocampus and the hemispheres but instead increased DOPAC levels in these brain regions as well as in the limbic forebrain. Yohimbine also markedly enhanced DOPA accumulation in the hippocampus and the hemispheres after inhibition of 1-aromatic amino acid decarboxylase by means of NSD 1015, whereas in the limbic system only a modest increase was obtained. The yohimbine-induced effects on the catecholamine synthesis rate were largely abolished in animals severely depleted of NA by means of 6-hydroxy-dopamine (6-OH-DA) pretreatment. Yohimbine decreased both the 5-HIAA/5-HT quotient (an indicator of 5-HT turnover) and 5-HTP accumulation after NSD 1015 in the hemispheres, whereas in the hippocampus and the limbic system only 5-HTP accumulation was decreased. The yohimbine-induced effect on the indoleamine synthesis rate was not influenced by 6-OH-DA pretreatment, whereas this effect and that on the catecholamine synthesis rate were both abolished by reserpine pretreatment. Neither in vivo nor in vitro administration of yohimbine significantly altered baseline or GABA-induced accumulation of 36Cl- in corticohippocampal synaptoneurosomes. In conclusion, the present study provides neurochemical support for the suggestion that yohimbine may exert its anticonflict effect in a modified Vogel's conflict test by increasing and decreasing NA and 5-HT neurotransmission, respectively, whereas no evidence was obtained for a direct interaction of yohimbine with GABAA/BDZ receptor function.