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Antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models.

Hajhashemi V, Dehdashti Kh - Res Pharm Sci (2014 Sep-Oct)

Bottom Line: Naloxone (5 mg/kg, i.p) was used to induce morphine withdrawal syndrome and the number of jumps and presence of ptosis, piloerection, tremor, sniffing and diarrhea were recorded and compared with control group.Clavulanic acid at doses of 10, 20 and 40 mg/kg inhibited abdominal constriction and licking behavior of acetic acid and formalin-induced pain respectively.Clavulanic acid has considerable antinociceptive activity and further studies are needed to clarify its exact mechanism.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

ABSTRACT
Glutamate has a key role in pain perception and also development of tolerance and dependence to morphine. It has been reported that clavulanic acid affects glutamatergic transmission via activation of glutamate transporter. Therefore the present study was aimed to evaluate the possible antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models. Male Swiss mice (25-30 g) were used in this study. Acetic acid-induced writhing, formalin test and hot plate method were used to assess the antinociceptive effect of clavulanic acid. Morphine (30 mg/kg, s.c.) was administered to the mice two times a day (8 AM and 4 PM) for 3 days in order to produce tolerance. To develop morphine dependence, morphine sulfate (50, 50 and 75 mg/kg) was injected at 8 and 12 AM and 16 PM respectively and for 3 consecutive days. Naloxone (5 mg/kg, i.p) was used to induce morphine withdrawal syndrome and the number of jumps and presence of ptosis, piloerection, tremor, sniffing and diarrhea were recorded and compared with control group. Clavulanic acid at doses of 10, 20 and 40 mg/kg inhibited abdominal constriction and licking behavior of acetic acid and formalin-induced pain respectively. Clavulanic acid was not able to show any antinociception in hot plate model and could not prevent development of tolerance and dependence to morphine. Clavulanic acid has considerable antinociceptive activity and further studies are needed to clarify its exact mechanism.

No MeSH data available.


Related in: MedlinePlus

Effect of clavulanic acid on development of tolerance to antinociceptive activity of morphine. Morphine (30 mg/kg, s.c.) was administered to mice two times a day (8 AM and 4 PM) for 3 days in order to produce tolerance. A group of animals (non-tolerant) received saline during these days. Thirty min before each morphine injection, mice were pretreated with clavulanic acid (50 or 100 mg/kg, i.p.) or vehicle. On day 4, antinociceptive tolerance to a challenge dose of morphine (5 mg/kg, s.c) was evaluated using the hot-plate test. Data are mean ± SEM of 6 animals in each group. *p<0.05, ***p<0.001 compared with control group.
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Figure 5: Effect of clavulanic acid on development of tolerance to antinociceptive activity of morphine. Morphine (30 mg/kg, s.c.) was administered to mice two times a day (8 AM and 4 PM) for 3 days in order to produce tolerance. A group of animals (non-tolerant) received saline during these days. Thirty min before each morphine injection, mice were pretreated with clavulanic acid (50 or 100 mg/kg, i.p.) or vehicle. On day 4, antinociceptive tolerance to a challenge dose of morphine (5 mg/kg, s.c) was evaluated using the hot-plate test. Data are mean ± SEM of 6 animals in each group. *p<0.05, ***p<0.001 compared with control group.

Mentions: As it is seen in Fig. 5, three days treatment of morphine induced tolerance as compared with the group received vehicle during these days. In morphine tolerant group, the antinociceptive activity of morphine was significantly (p<0.05) less than non-tolerant animals. Pretreatment of animals with clavulanic acid (50 or 100 mg/kg, i.p.) could not reverse the development of tolerance.


Antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models.

Hajhashemi V, Dehdashti Kh - Res Pharm Sci (2014 Sep-Oct)

Effect of clavulanic acid on development of tolerance to antinociceptive activity of morphine. Morphine (30 mg/kg, s.c.) was administered to mice two times a day (8 AM and 4 PM) for 3 days in order to produce tolerance. A group of animals (non-tolerant) received saline during these days. Thirty min before each morphine injection, mice were pretreated with clavulanic acid (50 or 100 mg/kg, i.p.) or vehicle. On day 4, antinociceptive tolerance to a challenge dose of morphine (5 mg/kg, s.c) was evaluated using the hot-plate test. Data are mean ± SEM of 6 animals in each group. *p<0.05, ***p<0.001 compared with control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317999&req=5

Figure 5: Effect of clavulanic acid on development of tolerance to antinociceptive activity of morphine. Morphine (30 mg/kg, s.c.) was administered to mice two times a day (8 AM and 4 PM) for 3 days in order to produce tolerance. A group of animals (non-tolerant) received saline during these days. Thirty min before each morphine injection, mice were pretreated with clavulanic acid (50 or 100 mg/kg, i.p.) or vehicle. On day 4, antinociceptive tolerance to a challenge dose of morphine (5 mg/kg, s.c) was evaluated using the hot-plate test. Data are mean ± SEM of 6 animals in each group. *p<0.05, ***p<0.001 compared with control group.
Mentions: As it is seen in Fig. 5, three days treatment of morphine induced tolerance as compared with the group received vehicle during these days. In morphine tolerant group, the antinociceptive activity of morphine was significantly (p<0.05) less than non-tolerant animals. Pretreatment of animals with clavulanic acid (50 or 100 mg/kg, i.p.) could not reverse the development of tolerance.

Bottom Line: Naloxone (5 mg/kg, i.p) was used to induce morphine withdrawal syndrome and the number of jumps and presence of ptosis, piloerection, tremor, sniffing and diarrhea were recorded and compared with control group.Clavulanic acid at doses of 10, 20 and 40 mg/kg inhibited abdominal constriction and licking behavior of acetic acid and formalin-induced pain respectively.Clavulanic acid has considerable antinociceptive activity and further studies are needed to clarify its exact mechanism.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

ABSTRACT
Glutamate has a key role in pain perception and also development of tolerance and dependence to morphine. It has been reported that clavulanic acid affects glutamatergic transmission via activation of glutamate transporter. Therefore the present study was aimed to evaluate the possible antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models. Male Swiss mice (25-30 g) were used in this study. Acetic acid-induced writhing, formalin test and hot plate method were used to assess the antinociceptive effect of clavulanic acid. Morphine (30 mg/kg, s.c.) was administered to the mice two times a day (8 AM and 4 PM) for 3 days in order to produce tolerance. To develop morphine dependence, morphine sulfate (50, 50 and 75 mg/kg) was injected at 8 and 12 AM and 16 PM respectively and for 3 consecutive days. Naloxone (5 mg/kg, i.p) was used to induce morphine withdrawal syndrome and the number of jumps and presence of ptosis, piloerection, tremor, sniffing and diarrhea were recorded and compared with control group. Clavulanic acid at doses of 10, 20 and 40 mg/kg inhibited abdominal constriction and licking behavior of acetic acid and formalin-induced pain respectively. Clavulanic acid was not able to show any antinociception in hot plate model and could not prevent development of tolerance and dependence to morphine. Clavulanic acid has considerable antinociceptive activity and further studies are needed to clarify its exact mechanism.

No MeSH data available.


Related in: MedlinePlus