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Journal of Pharmacology and Experimental Therapeutics

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OtherNEUROPHARMACOLOGY

Activation of the Locus Coeruleus Noradrenergic System by Intracoerulear Microinfusion of Corticotropin-Releasing Factor: Effects on Discharge Rate, Cortical Norepinephrine Levels and Cortical Electroencephalographic Activity

Andre L. Curtis, Sandra M. Lechner, Luis A. Pavcovich and Rita J. Valentino
Journal of Pharmacology and Experimental Therapeutics April 1997, 281 (1) 163-172;
Andre L. Curtis
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Sandra M. Lechner
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Luis A. Pavcovich
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Rita J. Valentino
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Abstract

Corticotropin-releasing factor (CRF) administered intracerebroventricularly (i.c.v.) activates noradrenergic locus coeruleus (LC) neurons of halothane-anesthetized and unanesthetized rats. This study used a technique for microinfusing CRF into the LC from calibrated micropipettes to characterize and quantify the effects of locally administered CRF on LC discharge in halothane-anesthetized rats. CRF (3–100 ng) microinfusion into the LC increased discharge rate in a dose-dependent manner from 28 ± 8 to 105 ± 26% above preinfusion discharge rates. The CRF dose-response curve generated by local microinfusion was parallel to, and shifted approximately 200-fold to the left, of that generated by i.c.v. administration. Intracoerulear microinfusion of the CRF antagonist, [DPhe12,Nle21,38,CαMeLeu37]r/hCRF(12–41),greatly attenuated LC activation produced by a maximally effective dose of i.c.v. administered CRF, suggesting that these effects are primarily due to actions within the LC. In rats in which both LC discharge rate and norepinephrine levels in prefrontal cortex were measured byin vivo microdialysis, CRF microinfused into the LC increased both endpoints. Finally, LC activation produced by CRF (60 ng) microinfusion into the LC was associated with cortical electroencephalographic activation. Taken together with previous anatomical and electrophysiological evidence for endogenous CRF interactions in the LC, our results support the hypothesis that CRF serves as an excitatory neurotransmitter in the LC, and suggest that its actions on LC neurons are translated to enhanced norepinephrine release and an impact on cortical targets.

Footnotes

  • Send reprint requests to: Dr. Rita J. Valentino, Department of Psychiatry, Allegheny University, Broad and Vine Sts., Philadelphia, PA 19102-1192.

  • ↵1 This work was supported by USPHS Grants MH40008 and MH00840 (an RSDA award to R.J.V.).

  • Abbreviations:
    ACSF
    artificial cerebrospinal fluid
    CRF
    corticotropin-releasing factor
    DPheCRF12–41
    [DPhe12,Nle21,38,CαMeLeu37]r/hCRF(12–41)
    EEG
    electroencephalographic activity
    i.c.v.
    intracerebroventricular
    LC
    locus coeruleus
    PSA
    power spectrum analysis
    PSB
    Pontamine sky blue
    • Received April 24, 1996.
    • Accepted December 24, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 281, Issue 1
1 Apr 1997
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OtherNEUROPHARMACOLOGY

Activation of the Locus Coeruleus Noradrenergic System by Intracoerulear Microinfusion of Corticotropin-Releasing Factor: Effects on Discharge Rate, Cortical Norepinephrine Levels and Cortical Electroencephalographic Activity

Andre L. Curtis, Sandra M. Lechner, Luis A. Pavcovich and Rita J. Valentino
Journal of Pharmacology and Experimental Therapeutics April 1, 1997, 281 (1) 163-172;

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OtherNEUROPHARMACOLOGY

Activation of the Locus Coeruleus Noradrenergic System by Intracoerulear Microinfusion of Corticotropin-Releasing Factor: Effects on Discharge Rate, Cortical Norepinephrine Levels and Cortical Electroencephalographic Activity

Andre L. Curtis, Sandra M. Lechner, Luis A. Pavcovich and Rita J. Valentino
Journal of Pharmacology and Experimental Therapeutics April 1, 1997, 281 (1) 163-172;
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