title: Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.
abstract: 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 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-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 μM), 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.
authors: Graduate Institute of Acupuncture Science, China Medical University, No. 91, Hsueh-Shih Road, Taichung, Taiwan.
authors: Y-H
authors: YH
authors: Chen
authors: P-L
authors: PL
authors: Lin
authors: R-W
authors: RW
authors: Wong
authors: Y-T
authors: YT
authors: Wu
authors: H-Y
authors: HY
authors: Hsu
authors: M-C
authors: MC
authors: Tsai
authors: M-J
authors: MJ
authors: Lin
authors: Y-C
authors: YC
authors: Hsu
authors: C-H
authors: CH
authors: Lin
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D017952:Ganglia, Invertebrate / Q000166:cytology; D008911:Minocycline / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012908:Snails; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D000697:Central Nervous System Stimulants; D026902:Potassium Channel Blockers; D005576:Colforsin; D003994:Bucladesine; D019789:Tetraethylammonium; D008911:Minocycline; D003913:Dextroamphetamine