Gabapentin completely attenuated the acute morphine induced c-Fos expression in the rat striatum.
The neuro-anatomical sites and molecular mechanism of action of gabapentin (GBP)-morphine interaction to prevent and reverse morphine side effects as well as enhancement of the analgesic effect of morphine is not known. Therefore, we examined the combined effects of GBP-Morphine on acute morphine induced c-Fos expression in rat striatum. The combined effect of GBP-Morphine was examined by means of c-Fos immunohistochemistry. A single intraperitoneal injection (i.p.) of morphine (10 mg/kg), saline (control), co-injection of GBP (150 mg/kg) with morphine (10 mg/kg) was administered under anaesthesia. Ninety minutes after drugs administration the deeply anesthetized rats were perfused transcardially with 4% paraformaldehyde. Serial 40 mum thick sections of brain were cut and processed by immunohistochemistry to locate and quantify the sites and number of neurons with c-Fos immunoreactivity. Detection of c-Fos protein was performed using the peroxidase-antiperoxidase (PAP) detection protocol. Our present study demonstrated that, administration of GBP (150 mg/kg, i.p.) in combination with morphine (10 mg/kg, i.p.) significantly (p < 0.01) attenuated the acute morphine (10 mg/kg, i.p.) induced c-Fos expression in the rat striatum. Present results showed that GBP-morphine combination action prevented the acute morphine induced c-Fos expression in rat striatum. Moreover, this study provides first evidence of neuro-anatomical site and that GBP neutralized the morphine induced activation of rat striatum.
Kazi
Jamil Ahsan
JA
Department of Anaesthesia, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. anaajk@nus.edu.sg
Gee
Chen Fun
CF
D000588:Amines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004347:Drug Interactions; D000077206:Gabapentin; D007150:Immunohistochemistry; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000588:Amines; D000700:Analgesics; D000701:Analgesics, Opioid; D003509:Cyclohexanecarboxylic Acids; D016760:Proto-Oncogene Proteins c-fos; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine