The effects of piperazine on rat sympathetic neurones

1. The neuronal effects of the anthelmintic piperazine (Pip) on rat sympathetic ganglia were studied in vitro by means of intracellular and extracellular recording techniques. 2. Surface potential recordings indicated that Pip (0.1-10 mM as citrate, 1-30 mM as hexahydrate) produced a sustained depolarization (reversible on washing) of rat ganglia. gamma-Aminobutyric acid (GABA, 1-100 micro M) also evoked reversible depolarizations but, unlike Pip, responses to the higher doses of GABA declined during a 2 min exposure. Depolarizations produced by Pip or carbachol (but not GABA) were markedly depressed by hexamethonium but only slightly by bicuculline or picrotoxin. 3. Intracellular recordings revealed that Pip-induced depolarizations were accompanied by an increase in membrane conductance and a broadening and depression of the directly-evoked spike. 4. In the presence of hexamethonium (1 mM), the responses to Pip hexahydrate and to cholinoceptor agonists were abolished, but Pip citrate still changed the spike configuration and induced membrane hyperpolarization with a small conductance increase. These residual effects were mimicked by superfusing with Na citrate or Ca2+-free medium, suggesting that significant Ca2+ binding by the citrate anion of the Pip salt was probably responsible for the observed activity of Pip citrate in the presence of hexamethonium. 5. It is concluded that on rat ganglia Pip is a nicotinic agonist, with no detectable GABA-mimetic activity.