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Central administration of histamine H1 receptor agonist, fMPH, blocks olanzapineinduced activation of ampk-cpt1 signaling in the dorsal vagal complex in rats

Conference Paper


Abstract


  • Olanzapine treatment is associated with severe obesity. The AMPactivated

    protein kinase (AMPK) in the dorsal vagal complex (DVC)

    plays an important role in feeding regulation, which can regulate energy

    balance through modulating acetyl-CoA carboxylase (ACC)-carnitine

    palmitoyltransferase 1 (CPT1) signaling. Histamine H1 receptor (H1R)

    antagonism acts as a key contributor for olanzapine-induced obesity.

    Aim: To investigate the effect of olanzapine on food intake and DVC

    AMPK-CPT1 signaling, and whether these effects could be blocked by

    central H1R activation. Methods: Rats were treated with olanzapine

    (1 mg/kg, t.i.d., orally, n=5-8/group) or vehicle for 4 days. On day

    5th, different doses (200nM or 100nM) of 2-(3-trifluoromethylphenyl)

    histamine (FMPH, H1R agonist), or saline was centrally injected before

    olanzapine or vehicle was given. Cumulative food intake was measured.

    After 3 days drug wash out period, the treatment was repeated and

    rats were sacrificed, and DVC tissues were collected for the detection

    of phosphor-AMPK, phosphor-ACC levels and CPT1 activity. Results:

    Olanzapine-induced hyperphagia after 4 days treatment was significantly

    reduced by FMPH in a dose-dependent manner up to 16hrs (p<0.05). The

    DVC phosphor-AMPK and phosphor-ACC levels as well as CPT1 activity

    was significantly increased by olanzapine (p<0.05). The stimulatory effect

    of olanzapine on phosphor-AMPK tended to be blocked by FMPH 200nM

    (p=0.06). The up-regulated CPT1 activity induced by olanzapine was

    significantly inhibited by FMPH 200nM (p<0.05). Conclusion: These

    findings indicated that activation of AMPK-CPT1 signaling induced by

    H1R antagonism may play an important role in olanzapine-induced

    hyperphagia.

Publication Date


  • 2013

Citation


  • He, M., Zhang, Q., Wang, H., Deng, C. & Huang, X. -F. (2013). Central administration of histamine H1 receptor agonist, fMPH, blocks olanzapineinduced activation of ampk-cpt1 signaling in the dorsal vagal complex in rats. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 120-120). Australia: ANS.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/904

Start Page


  • 120

End Page


  • 120

Place Of Publication


  • Australia

Abstract


  • Olanzapine treatment is associated with severe obesity. The AMPactivated

    protein kinase (AMPK) in the dorsal vagal complex (DVC)

    plays an important role in feeding regulation, which can regulate energy

    balance through modulating acetyl-CoA carboxylase (ACC)-carnitine

    palmitoyltransferase 1 (CPT1) signaling. Histamine H1 receptor (H1R)

    antagonism acts as a key contributor for olanzapine-induced obesity.

    Aim: To investigate the effect of olanzapine on food intake and DVC

    AMPK-CPT1 signaling, and whether these effects could be blocked by

    central H1R activation. Methods: Rats were treated with olanzapine

    (1 mg/kg, t.i.d., orally, n=5-8/group) or vehicle for 4 days. On day

    5th, different doses (200nM or 100nM) of 2-(3-trifluoromethylphenyl)

    histamine (FMPH, H1R agonist), or saline was centrally injected before

    olanzapine or vehicle was given. Cumulative food intake was measured.

    After 3 days drug wash out period, the treatment was repeated and

    rats were sacrificed, and DVC tissues were collected for the detection

    of phosphor-AMPK, phosphor-ACC levels and CPT1 activity. Results:

    Olanzapine-induced hyperphagia after 4 days treatment was significantly

    reduced by FMPH in a dose-dependent manner up to 16hrs (p<0.05). The

    DVC phosphor-AMPK and phosphor-ACC levels as well as CPT1 activity

    was significantly increased by olanzapine (p<0.05). The stimulatory effect

    of olanzapine on phosphor-AMPK tended to be blocked by FMPH 200nM

    (p=0.06). The up-regulated CPT1 activity induced by olanzapine was

    significantly inhibited by FMPH 200nM (p<0.05). Conclusion: These

    findings indicated that activation of AMPK-CPT1 signaling induced by

    H1R antagonism may play an important role in olanzapine-induced

    hyperphagia.

Publication Date


  • 2013

Citation


  • He, M., Zhang, Q., Wang, H., Deng, C. & Huang, X. -F. (2013). Central administration of histamine H1 receptor agonist, fMPH, blocks olanzapineinduced activation of ampk-cpt1 signaling in the dorsal vagal complex in rats. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 120-120). Australia: ANS.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/904

Start Page


  • 120

End Page


  • 120

Place Of Publication


  • Australia