Central regulation of adrenal tyrosine hydroxylase: interaction between dopamine and GABA systems

It has been previously demonstrated that nigrostriatal dopaminergic fibres participate in the neural regulation of the activity of adrenal tyrosine hydroxylase, specifically in its induction. To determine whether activation or inhibition of these fibres is responsible for this induction, the role of presynaptic dopamine receptors was investigated. Apomorphine (0.2 mg/kg), (+)3-PPP (10 mg/kg) and BHT 920 (1-3 mg/kg), drugs that are reported to bind to presynaptic dopamine receptors and thereby inhibit the release of that neurotransmitter, caused significant increases in the activity of the enzyme. As a central GABA (gamma-aminobutyric acid) system is believed to exert inhibitory control over the release of dopamine, GABA agonists were also tested for their effects. Muscimol (3 mg/kg), gamma-hydroxybutyrate (500 mg/kg) and HA-966 (150 mg/kg) produced significant induction of the adrenal enzyme; this induction was not blocked by dopamine postsynaptic receptor antagonists. After intraventricular administration (5 micrograms/rat) in normal animals, HA-966 produced significant induction of tyrosine hydroxylase. Its systemic administration did not induce the enzyme in animals with the adrenal denervated. When administered together at submaximal doses, HA-966 and BHT 920 produced an additive effect in the induction of adrenal tyrosine hydroxylase.