ABSTRACT
Glutamate (Glu) is considered the most important excitatory amino acid neurotransmitter in the mammalian Central Nervous System. Zinc (Zn) is co-released with Glu during synaptic transmission and interacts with Glutamate receptors and transporters. We performed binding experiments using [3H]MK-801 (NMDA), and [3H]Fluorowillardine (AMPA) as ligands to study Zn-Glutamate interactions in rat cortical synaptic membranes. We also examined the effects of mercury and lead on NMDA or AMPA receptors. Zinc at 1 nM, significantly potentiates [3H]MK-801 binding. Lead inhibits [3H]MK-801 binding at micromolar concentrations. At millimolar concentrations, Hg also has a significant inhibitory effect. These effects are not reversed by Zn (1 nM). Zinc displaces the [3H]FW binding curve to the right. Lead (nM) and Hg (µM) inhibit [3H]FW binding. At certain concentrations, Zn reverses the effects of these metals on [3H]FW binding. These specific interactions serve to clarify the role of Zn, Hg, and Pb in physiological and pathological conditions.
Subject(s)
Alanine/analogs & derivatives , Dizocilpine Maleate/metabolism , Lead/pharmacology , Mercury/pharmacology , Pyrimidines/metabolism , Synaptic Membranes/metabolism , Zinc/pharmacology , Alanine/metabolism , Animals , Neuroprotective Agents/metabolism , Rats , Synaptic Membranes/drug effectsABSTRACT
Cocaine sensitization results in the development of increased locomotion and stereotypy. It is accompanied by changes in glutamatergic trasmission that appear to be region-specific. The purpose of this article was to determine the effect(s) of cocaine and prazosin plus cocaine treatments on ionotropic glutamate receptors in rat cerebral cortex (CTX) and prefrontal cortex (PFC). Cocaine-sensitized rats (15 mg/kg, i.p. once for 5 days), withdrawn (7 days) and later challenged with a single cocaine dose, showed region-specific in NMDA-2A and Glu-R2 in the CTX and PFC membranes in cocaine- and prazosin-treated rats when compared to the saline controls. Co-administration of prazosin inhibits sensitization and changes in NMDA 2A and Glu-R2. Furthermore, prazosin inhibits the effect of cocaine in CTX and PFC on [(3)H]FW (AMPA agonist) binding when compared to controls. In cortex, cocaine treatment causes a marked increase in total binding, while in PFC there is a significant decrease. In both regions, cocaine-prazosin treatment attenuates the effects of cocaine. These results suggest that cocaine affects ionotropic glutamate receptors (NMDA and AMPA) and that prazosin inhibits such effects in a region-specific form in rat brain.
