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Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice

View Article: PubMed Central - PubMed

ABSTRACT

Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

No MeSH data available.


Effect of MMC and ACAM on the extinction of ethanol CPP in mice. Data are expressed as the mean difference between the times spent in the compartment paired with ethanol and the times spent in the compartment paired with saline (n = 7–9). Significant difference ##p < 0.01 was compared with the saline control group; ∗p < 0.05 and ∗∗p < 0.01 were compared with the vehicle control; when not indicated, the differences were not statistically significant.
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Figure 3: Effect of MMC and ACAM on the extinction of ethanol CPP in mice. Data are expressed as the mean difference between the times spent in the compartment paired with ethanol and the times spent in the compartment paired with saline (n = 7–9). Significant difference ##p < 0.01 was compared with the saline control group; ∗p < 0.05 and ∗∗p < 0.01 were compared with the vehicle control; when not indicated, the differences were not statistically significant.

Mentions: The effect of MMC and ACAM on the extinction of ethanol-induced CPP is shown in Figure 3. ANOVA results revealed significant effects of Group [F(5,221) = 32.0; P < 0.001], Trial [F(5,221) = 4.16; P < 0.05], and a Group × Trial interaction [F(5,221) = 4.43; P < 0.001]. Separate One-way ANOVA on the data from each extinction trial revealed that there was a significant difference in conditioning score on extinction days: Ext 1, Ext 3, and Ext 5 [F(5,35) = 31.3, p < 0.001; F(5,35) = 9.28, p < 0.001; F(5,35) = 36.2, p < 0.001, respectively]. The vehicle control group showed a marked preference for the ethanol-paired compartment from Ext 1–7, after that it performed no differently than the saline control group. Interestingly, MMC (3 and 5 g/kg, p.o.), ACAM (300 mg/kg, p.o.) showed a marked accelerating effect on the extinction of ethanol CPP (Figure 3). The post hoc analysis revealed that MMC significantly reduced the conditioning score at a dose of 5 g/kg during extinction 1–7 and at a dose of 3 g/kg from extinction 1–5, when compared with the vehicle control group. Similarly, acamprosate (300 mg/kg, p.o.) treated animals showed significant reduction in conditioning score during extinction phase (Ext 1–5). However, MMC at a dose of 1 g/kg did not reduce the preference for the ethanol-paired environment across the entire extinction phase.


Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice
Effect of MMC and ACAM on the extinction of ethanol CPP in mice. Data are expressed as the mean difference between the times spent in the compartment paired with ethanol and the times spent in the compartment paired with saline (n = 7–9). Significant difference ##p < 0.01 was compared with the saline control group; ∗p < 0.05 and ∗∗p < 0.01 were compared with the vehicle control; when not indicated, the differences were not statistically significant.
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Figure 3: Effect of MMC and ACAM on the extinction of ethanol CPP in mice. Data are expressed as the mean difference between the times spent in the compartment paired with ethanol and the times spent in the compartment paired with saline (n = 7–9). Significant difference ##p < 0.01 was compared with the saline control group; ∗p < 0.05 and ∗∗p < 0.01 were compared with the vehicle control; when not indicated, the differences were not statistically significant.
Mentions: The effect of MMC and ACAM on the extinction of ethanol-induced CPP is shown in Figure 3. ANOVA results revealed significant effects of Group [F(5,221) = 32.0; P < 0.001], Trial [F(5,221) = 4.16; P < 0.05], and a Group × Trial interaction [F(5,221) = 4.43; P < 0.001]. Separate One-way ANOVA on the data from each extinction trial revealed that there was a significant difference in conditioning score on extinction days: Ext 1, Ext 3, and Ext 5 [F(5,35) = 31.3, p < 0.001; F(5,35) = 9.28, p < 0.001; F(5,35) = 36.2, p < 0.001, respectively]. The vehicle control group showed a marked preference for the ethanol-paired compartment from Ext 1–7, after that it performed no differently than the saline control group. Interestingly, MMC (3 and 5 g/kg, p.o.), ACAM (300 mg/kg, p.o.) showed a marked accelerating effect on the extinction of ethanol CPP (Figure 3). The post hoc analysis revealed that MMC significantly reduced the conditioning score at a dose of 5 g/kg during extinction 1–7 and at a dose of 3 g/kg from extinction 1–5, when compared with the vehicle control group. Similarly, acamprosate (300 mg/kg, p.o.) treated animals showed significant reduction in conditioning score during extinction phase (Ext 1–5). However, MMC at a dose of 1 g/kg did not reduce the preference for the ethanol-paired environment across the entire extinction phase.

View Article: PubMed Central - PubMed

ABSTRACT

Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

No MeSH data available.