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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 naloxone-induced jumping behavior of morphine dependent mice. To develop morphine dependence, three groups of mice (n=6) received morphine sulfate (50, 50 and 75 mg/kg) at 8 and 12 AM and 16 PM respectively and for 3 consecutive days. A dose of 50 mg/ kg of morphine sulfate was also injected on the 4th day. Clavulanic acid (50 and 100 mg/kg, i.p.) was administered from second day and 30 min prior to morphine injections. Control group was injected with saline (10 ml/kg, i.p.) instead of clavulanic acid. Naloxone (5 mg/kg, i.p.) was injected 2 h after the last morphine injection, and the number of jumps was counted immediately after naloxone injection over a 30 min period. Data are mean ± SEM of 6 animals in each group.
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Figure 6: Effect of clavulanic acid on naloxone-induced jumping behavior of morphine dependent mice. To develop morphine dependence, three groups of mice (n=6) received morphine sulfate (50, 50 and 75 mg/kg) at 8 and 12 AM and 16 PM respectively and for 3 consecutive days. A dose of 50 mg/ kg of morphine sulfate was also injected on the 4th day. Clavulanic acid (50 and 100 mg/kg, i.p.) was administered from second day and 30 min prior to morphine injections. Control group was injected with saline (10 ml/kg, i.p.) instead of clavulanic acid. Naloxone (5 mg/kg, i.p.) was injected 2 h after the last morphine injection, and the number of jumps was counted immediately after naloxone injection over a 30 min period. Data are mean ± SEM of 6 animals in each group.

Mentions: Treatment of dependent mice with naloxone induced withdrawal syndrome characterized with jumping, piloerection, tremor, diarrhea and ptosis. Clavulanic acid (50 or 100 mg/kg, i.p.) did not exert any significant change in the number of jumpings (Fig. 6). In addition, pretreatment with clavulanic acid could not suppress other symptoms of withdrawal syndrome (Data not shown).


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 naloxone-induced jumping behavior of morphine dependent mice. To develop morphine dependence, three groups of mice (n=6) received morphine sulfate (50, 50 and 75 mg/kg) at 8 and 12 AM and 16 PM respectively and for 3 consecutive days. A dose of 50 mg/ kg of morphine sulfate was also injected on the 4th day. Clavulanic acid (50 and 100 mg/kg, i.p.) was administered from second day and 30 min prior to morphine injections. Control group was injected with saline (10 ml/kg, i.p.) instead of clavulanic acid. Naloxone (5 mg/kg, i.p.) was injected 2 h after the last morphine injection, and the number of jumps was counted immediately after naloxone injection over a 30 min period. Data are mean ± SEM of 6 animals in each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Effect of clavulanic acid on naloxone-induced jumping behavior of morphine dependent mice. To develop morphine dependence, three groups of mice (n=6) received morphine sulfate (50, 50 and 75 mg/kg) at 8 and 12 AM and 16 PM respectively and for 3 consecutive days. A dose of 50 mg/ kg of morphine sulfate was also injected on the 4th day. Clavulanic acid (50 and 100 mg/kg, i.p.) was administered from second day and 30 min prior to morphine injections. Control group was injected with saline (10 ml/kg, i.p.) instead of clavulanic acid. Naloxone (5 mg/kg, i.p.) was injected 2 h after the last morphine injection, and the number of jumps was counted immediately after naloxone injection over a 30 min period. Data are mean ± SEM of 6 animals in each group.
Mentions: Treatment of dependent mice with naloxone induced withdrawal syndrome characterized with jumping, piloerection, tremor, diarrhea and ptosis. Clavulanic acid (50 or 100 mg/kg, i.p.) did not exert any significant change in the number of jumpings (Fig. 6). In addition, pretreatment with clavulanic acid could not suppress other symptoms of withdrawal syndrome (Data not shown).

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