Gabapentin completely attenuated the acute morphine-induced c-Fos expression in the rat nucleus accumbens.
A growing body of evidence suggests the existence of a functional interaction between gabapentin (GBP)-morphine system. However, the neuro-anatomical sites and molecular mechanism of action of gabapentin-morphine interaction to prevent and reverse morphine side effects as well as enhancement of the analgesic effect of morphine is not clear. Therefore, we examined the combined effects of GBP-morphine on acute morphine-induced c-Fos expression in rat nucleus accumbens. 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), and co-injection of GBP (150 mg/kg) with morphine (5 mg/kg) was administered under anesthesia. The deeply anesthetized rats were perfused transcardially with 4% paraformaldehyde 2 h after drugs administration. Serial 40 μm 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 detection protocol. The present study demonstrated that, administration of GBP (150 mg/kg, i.p.) in combination with morphine (5 mg/kg, i.p.) significantly (p < 0.01) attenuated the acute morphine (5 mg/kg, i.p.)-induced c-Fos expression in the rat nucleus accumbens shell. Present results showed that GBP-morphine combination action prevented the acute morphine-induced c-Fos expression in rat nucleus accumbens. Moreover, this study provides first evidence of neuro-anatomical site and that GBP neutralized the morphine-induced activation of rat nucleus accumbens shell.
Kazi
Jamil Ahsan
JA
Faculty of Dentistry, Universiti Teknologi MARA (UiTM), Level 19, Tower 2, Science & Technology Complex, 40450 Shah Alam, Selangor D.E, Malaysia. kazi@salam.uitm.edu.my
Abu-Hassan
Mohamed Ibrahim
MI
D000588:Amines / Q000378:metabolism / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000378:metabolism / Q000494:pharmacology*; D000077206:Gabapentin; D008297:Male; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D000588:Amines; D000701:Analgesics, Opioid; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D016760:Proto-Oncogene Proteins c-fos; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine