The effect of drugs which alter GABA-ergic function on cerebellar guanosine-3′, 5′-monophosphate content

The actions of several classes of drugs, thought to be involved with gamma-amino-butyric acid (GABA) mechanisms, have been examined for effects on cerebellar cGMP content. Picrotoxin and TRH increased, while ethanol and diazepam decreased, cerebellar cGMP. Doses of gamma-hydroxybutyrate (GHB) and baclofen caused no significant effect at doses that caused behavioral changes. These cGMP actions were contrasted with those induced by the dopaminergic agents, apomorphine and haloperidol, which respectively, raised and lowered cerebellar cGMP. Apomorphine-induced increases in cGMP were blocked by haloperidol, but not by GHB or baclofen given eight min before sacrifice. However, baclofen given one hour before sacrifice caused effects similar to those of haloperidol. These results are discussed in terms of dopaminergic-GABAergic interactions.