Ketanserin reverses dizocilpine-suppression of morphine dependence but not tolerance in mice.
The present study investigated the effect of co-administration of ketanserin, a 5-HT(2A) receptor antagonist and dizocilpine, a non-competitive NMDA receptor antagonist on the development of tolerance and dependence to morphine in mice. Animals developed tolerance to the antinociceptive effect of morphine (10 mg/kg, twice daily) on day 3 and the degree of tolerance was further enhanced on day 9 and 10. Dizocilpine (0.2 mg/kg, twice daily for 9 days) prevented the development of tolerance to the antinociceptive effect of morphine. Dizocilpine (0.2 mg/kg) or combination of dizocilpine (0.2 mg/kg) and ketanserin (0.5, 1 and 2 mg/kg) acutely on day 10 did not affect morphine tolerance. Ketanserin (0.5, 1 and 2 mg/kg, twice daily for 9 days) pre-treatment failed to reverse the effect of dizocilpine on morphine tolerance. Dizocilpine (0.2 mg/kg, twice daily for 9 days) suppressed the development of morphine dependence as assessed by naloxone (2 mg/kg)-precipitated withdrawal jumps and diarrhea on day 10 of testing. Similarly, dizocilpine (0.2 mg/kg) acutely on day 10 suppressed the development of morphine dependence. Ketanserin (0.5, 1 and 2 mg/kg, twice daily for 9 days and acutely on day 10) pre-treatment reversed the effect of dizocilpine on morphine dependence. Ketanserin (0.5, 1 and 2 mg/kg, twice daily for 9 days) did not affect development of morphine tolerance and dependence. The present study demonstrated that ketanserin, a 5-HT(2A) receptor antagonist reversed the effect of dizocilpine on morphine dependence. This study gives behavioral evidence to the hypothesis that 5-HT(2A) receptor antagonists facilitate NMDA neurotransmission.
Ninan
I
I
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India.
Kulkarni
S K
SK
D000818:Animals; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004338:Drug Combinations; D004361:Drug Tolerance / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007650:Ketanserin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009021:Morphine Dependence / Q000503:physiopathology* / Q000517:prevention & control; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology
D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D009270:Naloxone; D016291:Dizocilpine Maleate; D007650:Ketanserin