The acute effects of 6-hydroxydopamine treatment on noradrenergic function in the rat hippocampus in vitro.
The electrophysiological consequences of in vitro treatment with 6-hydroxydopamine (6-OHDA) were examined in the CA1 region of the rat hippocampal slice. In control slices, norepinephrine (NE) increased the amplitude of the population spike response elicited by synaptic stimulation of hippocampal pyramidal neurons with a threshold of approximately 5 microM. When hippocampal slices were pretreated with 500 microM 6-OHDA for 10 min, perfusion with a subthreshold concentration of NE (0.5 microM) produced responses similar to those observed with a 10-fold higher concentration of NE in untreated slices. Baseline electrophysiological responses were unchanged following the 6-OHDA exposure. The potentiation of the response to NE by in vitro pretreatment with 6-OHDA was accompanied by a greater than 40% decrease in NE content and greater than 90% decrease in [3H]NE accumulation. In vivo treatment with 6-OHDA or N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) also potentiated the electrophysiological response to NE in a manner similar to that observed with acute in vitro 6-OHDA pretreatment. This action does not appear to be due to development of beta-adrenergic receptor supersensitivity, because the apparent potency of isoproterenol in increasing the population spike amplitude was unaffected. These data suggest that the increase in the potency of NE in slices pretreated with 6-OHDA is due to the rapid disruption of the high-affinity NE uptake mechanism characteristic of noradrenergic nerve terminals.
D000320:Adrenergic Fibers / Q000187:drug effects; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D006892:Hydroxydopamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D001596:Benzylamines; D006892:Hydroxydopamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D000242:Cyclic AMP; C012102:DSP 4; D009638:Norepinephrine