title: Ascorbic Acid inhibits development of tolerance and dependence to opiates in mice: possible glutamatergic or dopaminergic modulation.
abstract: In a recent study, it has been demonstrated that ascorbic acid possessed antidopaminergic activity and modulate the glutamatergic neurotransmission in mice. With this background, the present study was undertaken to study the effect of ascorbic acid on the development of tolerance and dependence to opiate and its mechanism of action. Male Swiss mice weighing 20-25 g were used in the present study. Mice were made physically dependent on opioid by the chronic administration of morphine (10 mg/kg, twice a day, for 9 days) intraperitoneally. Ascorbic acid, haloperidol (dopamine antagonist) or MK 801 (NMDA receptor antagonist) was administered daily for 9 d before challenging the animals with morphine. The development of tolerance was assessed by noting the tail-flick latency on day 1, 3, 9 and 10. On the 10(th) day after the measurement of tail-flick latency, animals were challenged with naloxone (2 mg/kg., i.p.) and incidence of escape jumps were recorded by placing the animals in 45 cm high plexiglass container. Ascorbic acid (400-1600 mg/kg) dose dependently inhibited development of tolerance and dependence to morphine as noted from tail-flick latency. When given along with MK 801 (0.01 mg/kg., i.p) or haloperidol (0.1 mg/kg i.p.), ascorbic acid (800 mg/kg., i.p.) potentiated the response of MK 801 or haloperidol. In conclusion, it is hypothesized that inhibition of development of tolerance and dependence to morphine by ascorbic acid appears to have two components, namely dopaminergic and glutamatergic.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh - 160 014, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Kulkarni
authors.forename: C
authors.initials: C
authors.lastname: Deshpande
authors.forename: A
authors.initials: A
authors.lastname: Dhir
references.citation: Indian J Exp Biol. 1993 May;31(5):435-9
references.pmid: 8359850
references.citation: Psychopharmacologia. 1973;32(2):113-20
references.pmid: 4796281
references.citation: Life Sci. 1975 Jul 1;17(1):35-40
references.pmid: 238090
references.citation: Science. 1991 Jan 4;251(4989):85-7
references.pmid: 1824728
references.citation: Neuropharmacology. 1983 Aug;22(8):939-43
references.pmid: 6312359
references.citation: Science. 1985 Jan 25;227(4685):438-40
references.pmid: 4038426
references.citation: Brain Res. 1991 Apr 26;547(1):77-81
references.pmid: 1860074
references.citation: Pharmacology. 2006;77(1):38-45
references.pmid: 16569938
references.citation: Neuroreport. 1990 Nov-Dec;1(3-4):194-6
references.pmid: 1983355
references.citation: Life Sci. 1992;51(12):921-30
references.pmid: 1355577
references.citation: Gen Pharmacol. 1995 Jan;26(1):131-6
references.pmid: 7713352
references.citation: Life Sci. 1989;45(7):599-606
references.pmid: 2671566
references.citation: Neurosci Lett. 1984 Dec 21;52(3):227-33
references.pmid: 6521967
references.citation: Pharmacol Rev. 1994 Sep;46(3):293-324
references.pmid: 7831382
references.citation: Life Sci. 1980 Jul 21;27(3):185-8
references.pmid: 7401932
references.citation: Neuropharmacology. 1983 Jan;22(1):135-7
references.pmid: 6843783
references.citation: Eur J Pharmacol. 1991 May 2;197(1):9-16
references.pmid: 1832640
references.citation: Life Sci. 1978 Jan;22(1):133-6
references.pmid: 564436
references.citation: Life Sci. 1976 Jan 15;18(2):163-7
references.pmid: 943681
references.citation: Nature. 1978 Nov 9;276(5684):186-8
references.pmid: 216919
references.citation: Brain Res. 1994 Mar 14;639(2):269-74
references.pmid: 7911390
references.citation: Psychopharmacology (Berl). 2005 Aug;181(1):71-9
references.pmid: 15806417