AMPA and NMDA receptors in P2 fractions of cocaine and cocaine-prazosin-treated rats.
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 Cocaine-sensitized rats (15 mg/kg, i.p. once for 5 days), withdrawn (7 days) and later challenged with a single cocaine dose, showed region-specific in NMDA-2A and Glu-R2 in the CTX and PFC membranes in cocaine- and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.
Ortiz
J G
JG
Department of Pharmacology and Toxicology, School of Medicine, University of Puerto Rico, Medical Sciences Campus, P.O. Box 365067, San Juan, Puerto Rico 00936-5067, USA. jg_ortiz@yahoo.com
González-Cabrera
S
S
Rubio-Dávila
M
M
Tirado-Costacamps
A
A
Vázquez-Torres
R
R
Berríos-Cartagena
N
N
Silva
W I
WI
Jiménez-Rivera
C A
CA
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D003042:Cocaine; D011224:Prazosin