Adenosinergic modulation of 3alpha-hydroxy-5alpha-pregnan-20-one induced catalepsy in mice

Neurosteroid 3alpha, 5alpha THP, a positive allosteric modulator of the GABA(A) receptor Cl- ionophore complex, induces catalepsy-like dopamine antagonists, adenosine agonists or GABA agonists. Adenosine and dopamine receptors are co-localized on GABAergic neurons in the striatum and regulate GABA-mediated neurotransmission. Moreover, the antagonistic interactions between specific subtypes of adenosine and dopamine receptors are involved in motor depressant or motor stimulant effects of adenosine receptor agonists or antagonists, respectively. Such interaction may modulate neurosteroid-induced catalepsy.

This study examined the modulation of 3alpha, 5alpha THP-induced catalepsy by adenosinergic agents.

Catalepsy induced by 3alpha, 5alpha THP (2-8 microg, ICV) was assessed by bar test periodically up to 3 h in mice. Adenosine A1, A2A or A3 receptor agonists or antagonists were given IP or ICV prior to 3alpha, 5alpha THP. Some animals received IP dopamine D2 receptor agonist or antagonist 30 min prior to above combination treatment.

Adenosine A1, A2A, and A3 receptor agonists potentiated, whereas adenosine A2A receptor antagonists, but not A1 antagonists, reversed 3alpha, 5alpha THP-induced catalepsy. These effects of adenosine agonists and antagonists were abolished by prior administration of bromocriptine, the dopamine D2 receptor agonist and spiperone, the dopamine D2 receptor antagonist, respectively.

These findings suggest specific adenosine-dopamine receptor interaction in the striatum to modulate 3alpha, 5alpha THP-induced catalepsy.