Cocaine alters mu but not delta or kappa opioid receptor-stimulated in situ [35S]GTPgammaS binding in rat brain.
Chronic cocaine administration produces alterations in mu and kappa opioid receptor density as well as striatal and accumbens opioid-regulated adenylyl cyclase activity, suggesting a psychostimulant responsive interaction between opioidergic and dopaminergic systems. Stimulation of G-protein-coupled opioid receptors inhibits adenylyl cyclase production of cyclic AMP. The present study employed in situ [(35)S]GTPgammaS binding to measure opioid receptor-stimulated activation of G-proteins in response to acute and chronic cocaine exposure. Male Fischer rats received acute (1 or 3 days) or chronic (14 days) binge pattern cocaine administration. Three and 14 days of cocaine injections resulted in greater increases in the ability of the mu receptor agonist DAMGO to stimulate [(35)S]GTPgammaS binding in both the core and the shell of the nucleus accumbens, all regions of the caudate putamen and the cingulate cortex compared with saline-matched controls. The greatest increases in DAMGO-stimulated [(35)S]GTPgammaS binding were observed in the dorsal areas of the caudate putamen in animals that received 14 days of cocaine. No significant changes in delta (DPDPE), or kappa (dynorphin A(1-17)) receptor-stimulated [(35)S]GTPgammaS binding were found in any brain region in response to cocaine administration. These results demonstrate that binge pattern cocaine administration induce changes in mu but not delta or kappa opioid receptor-mediated G-protein activity. This study provides support for the hypothesis that the addictive properties of both psychostimulants and opiates may share common neurochemical signaling substrates.
Schroeder
Joseph A
JA
Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. jschroed@astro.temple.edu
Niculescu
Michelle
M
Unterwald
Ellen M
EM
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D013997:Time Factors
D000701:Analgesics, Opioid; D018765:Dopamine Uptake Inhibitors; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020962:Heterotrimeric GTP-Binding Proteins; D003042:Cocaine