Korean J Physiol Pharmacol.  2012 Dec;16(6):379-386. 10.4196/kjpp.2012.16.6.379.

Effect of Berberine on Depression- and Anxiety-Like Behaviors and Activation of the Noradrenergic System Induced by Development of Morphine Dependence in Rats

Affiliations
  • 1Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Korea. bombi@khu.ac.kr
  • 2The Graduate School of Basic Science of Oriental Medicine, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Korea.

Abstract

The purpose of this study was to evaluate whether berberine (BER) administration could attenuate depression- and anxiety-like behaviors and increase corticotrophin-releasing factor (CRF) and tyrosine hydroxylase (TH) expression following chronic morphine withdrawal in rats. Male rats were exposed to chronic, intermittent, escalating morphine (10~50 mg/kg) for 10 days. After the last morphine injection, depression- and anxiety-like beahvior associated with morphine discontinuation persisted for at least three days during withdrawal without any change in ambulatory activity. Daily BER administration significantly decreased immobility in the forced swimming test and increased open-arm exploration in the elevated plus maze test. BER administration also significantly blocked the increase in hypothalamic CRF expression and TH expression in the locus coeruleus (LC) and the decrease in hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression. Taken together, these findings demonstrated that BER administration significantly reduced morphine withdrawal-associated behaviors following discontinuation of repeated morphine administration in rats, possibly through modulation of hypothalamic CRF and the central noradrenergic system. BER may be a useful agent for treating or alleviating complex withdrawal symptoms and preventing morphine use relapses.

Keyword

Berberine; Corticotrophin-releasing factor; Depression; Morphine; Tyrosine hydroxylase

MeSH Terms

Animals
Berberine
Brain-Derived Neurotrophic Factor
Depression
Humans
Locus Coeruleus
Male
Morphine
Morphine Dependence
Rats
Recurrence
RNA, Messenger
Substance Withdrawal Syndrome
Swimming
Tyrosine 3-Monooxygenase
Berberine
Brain-Derived Neurotrophic Factor
Morphine
RNA, Messenger
Tyrosine 3-Monooxygenase

Figure

  • Fig. 1 Experimental schedule of morphine withdrawal-induced depression- and anxiety-like behaviors in rats.

  • Fig. 2 Changes in immobility time (A) and climbing time (B) in the forced swimming test after withdrawal from repeated saline or morphine administration. Rats were placed in plastic cylinders, and their behavior was recorded for 5 min at 24, 48, and 72 h following the last saline or morphine injection. The effect of BER on immobility time (C) and climbing time (D) in forced swimming test during morphine withdrawal is shown. **p<0.01 vs. SAL group; #p<0.05, ##p<0.01 vs. MOR group.

  • Fig. 3 Changes in anxiety like behavior in the elevated plus maze after withdrawal from repeated saline or morphine administration. Rats were placed in the center of the maze facing an enclosed arm, and their behavior was recorded for 5 min at 24, 48 and 72 h following the last saline or morphine injection. The percentage of time spent in open-arm exploration (A) and the number of entries into open-arms (B) in the elevated plus maze are shown. The effect of BER on the percentage of time spent in open-arm exploration (C) and the number of entries into open arms (D) during morphine withdrawal are presented. *p<0.05, **p<0.01, ***p<0.001 vs. SAL group; #p<0.05, ##p<0.01 vs. MOR group.

  • Fig. 4 Representative photomicrographs showing CRF expression in the paraventricular nucleus (PVN) of the hypothalamus and TH expression in the locus coeruleus (LC) (A). Effect of BER on the expression of CRF (B) and TH (C) after withdrawal from repeated saline or morphine administration. Cells of the hypothalamus area were counted as the CRF reactive cells, and cells of the LC area were counted as the TH reactive cells within actual square box of defined size (100×100 µm2). The scale bar represents 50 µm. **p<0.01, ***p<0.001 vs. SAL; #p<0.05, ##p<0.01 vs. MOR group.

  • Fig. 5 RT-PCR bands (A) and their relative intensities (B) of brain-derived neurotrophic factor (BDNF) mRNA in the rat hippocampus after withdrawal from repeated saline or morphine administration. **p<0.01 vs. SAL group; #p<0.05, ##p<0.01 vs. MOR group.


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