Cocaine increases immunoglobulin heavy chain binding protein and caspase-12 expression in the rat dorsal striatum.
BACKGROUND
Cocaine increases endoplasmic reticulum (ER) stress protein expression via glutamate and dopamine receptor activation in the dorsal striatum.


OBJECTIVE
The present study was performed to investigate ER stress response in the dorsal striatum in response to acute or repeated cocaine stimulation. It was hypothesized that cocaine upregulates the ER stress protein immunoglobulin heavy chain binding protein (BiP) and the ER stress-associated protein caspase-12 via N-methyl-D-aspartate (NMDA) and D1 dopamine receptor activation.


METHODS
Western immunoblot and immunohistochemical analyses were mainly performed to test this hypothesis in the rat dorsal striatum.


RESULTS
The results showed that BiP and caspase-12 immunoreactivities were significantly increased at 30, 60, and 120 min after acute or repeated intraperitoneal (i.p.) injections of three doses (10, 20, 40 mg/kg) of cocaine for seven consecutive days. Intrastriatal (i.s.) infusion of the selective NMDA antagonist MK801 (2 nmol) or AP5 (2 nmol) significantly attenuated the increase in the immunoreactivity of caspase-12 in the dorsal striatum induced by repeated, but not acute, cocaine (20 mg/kg) administration. However, i.p. injection of the selective D1 antagonist SCH23390 (0.1 mg/kg) significantly attenuated the increase in the immunoreactivity of caspase-12 in the dorsal striatum induced by both acute and repeated cocaine (20 mg/kg) stimulation.


CONCLUSIONS
These findings suggest that acute or repeated cocaine administration can cause ER stress response in the dorsal striatum in which NMDA and D1 dopamine receptors participate in the mediation of the process.
Ahn
Sung Min
SM
Division of Biological Sciences, Pusan National University, 30 Jangjeon-dong, Kumjeong-gu, Pusan, 609-735, South Korea.
Kim
Soo Woon
SW
Choe
Eun Sang
ES
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015153:Blotting, Western; D053454:Caspase 12 / Q000096:biosynthesis*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D018832:Molecular Chaperones / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D000091342:Endoplasmic Reticulum Chaperone BiP
D001552:Benzazepines; D053454:Caspase 12; D003042:Cocaine; D016291:Dizocilpine Maleate; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C506443:Casp12 protein, rat