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Cocaine alters mu but not delta or kappa opioid receptor‐stimulated in situ [ 35 S]GTPγS binding in rat brain
Author(s) -
Schroeder Joseph A.,
Niculescu Michelle,
Unterwald Ellen M.
Publication year - 2003
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10148
Subject(s) - opioidergic , damgo , gtpgammas , μ opioid receptor , nucleus accumbens , chemistry , dynorphin , medicine , adenylyl cyclase , opioid , endocrinology , κ opioid receptor , enkephalin , opioid receptor , ventral tegmental area , agonist , receptor , pharmacology , opioid peptide , dopamine , dopaminergic , (+) naloxone
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]GTPγS 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]GTPγS 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]GTPγS 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]GTPγS 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. Synapse 47:26–32, 2003. © 2002 Wiley‐Liss, Inc.