MINOCYCLINE INHIBITS D-AMPHETAMINE-ELICITED ACTION POTENTIAL BURSTS IN A CENTRAL SNAIL NEURON

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 mu M elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 mu M) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 mu M), an adenylate cyclase activator, and by dibutyryl cAMP (N-6,2'-O-Dibutyryladenosine 3'-5'-cyclic monophosphate; 1 mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 mu M) plus tetraethylammonium chloride (TEA; 5 mM) or co-administration of TEA (5 mM) plus dibutyryl cAMP (1 mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 mu M)-elicited action potential bursts. Notably, TEA (50 mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 mu M), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.