Elsevier

Neuropharmacology

Volume 23, Issue 3, March 1984, Pages 339-348
Neuropharmacology

Analeptic effects of centrally injected TRH and analogues of TRH in the pentobarbitone-anaesthetized rat

https://doi.org/10.1016/0028-3908(84)90197-7Get rights and content

Abstract

The effect of intracerebral injection of TRH and several biologically stable TRH analogues in the pentobarbitone anaesthetized rat was examined. Bilateral injection of TRH (5.0 μg total dose) and the analogues RX 77368 (0.01–1.0 μg), CG 3509 (0.1–1.0 μg), DN-1417 (1.0 μg) and MK-771 (1.0 μg) into the nucleus accumbens reduced the pentobarbitone-induced sleeping time. The TRH metabolite DKP (5 μg) had no effect on the sleeping time following intra-accumbens injection. Intra-septal injection of TRH (1.0–5.0 μg), RX 77368 (0.1–1.0 μg) and CG 3509 (0.1–1.0 μg) also reversed the pentobarbitone-induced sleeping time. In contrast, TRH (5 μg) injected into the striatum had no effect on the pentobarbitone-induced sleeping time, and CG 3509 (0.1 μg) and RX 77368 (0.1 μg) had weaker effects following intrastriatal injection compared to injection of these analogues into the nucleus accumbens and septum. Measurements of core temperature and respiration rate in rats following intra-accumbens or septal injection of TRH, CG 3509 and RX 77368 showed these peptides to reverse pentobarbitone-induced hypothermia and stimulate respiration rate. However, while intrastriatal injections of CG 3509 and RX 77368 caused an increase in respiration rate they had no effect on core temperature. These results suggest a close association between peptide-induced respiratory stimulation and reversal of pentobarbitone-induced anaesthesia. Since intra-accumbens and septal injection of dopamine (20–100 μg) failed to reverse anaesthesia, it is unlikely that the peptide-induced responses are mediated via dopamine release.

References (40)

  • P.W. Kalivas et al.

    Effect of septohippocampal lesions on thyrotrophin-releasing hormone antagonism of pentobarbital narcosis

    Brain Res.

    (1981)
  • G. Metcalf

    Regulatory peptides as a source of new drugs—the clinical prospects for analogues of TRH which are resistant to metabolic degradation

    Brain Res. Rev.

    (1982)
  • G. Metcalf et al.

    Neuropharmacological evaluation of RX 77368—a stabilized analogue of thyrotrophin-releasing hormone (TRH)

    Regul. Peptides

    (1982)
  • M. Miyamoto et al.

    Mesolimbic involvement in the locomotor stimulant action of TRH in rats

    Eur. J. Pharmac.

    (1977)
  • M. Miyamoto et al.

    Gamma-butyrolacetone-β-carbinyl-histidyl-prolinamide citrate (DN-1417): a novel TRH analogue with potent effects on the central nervous system

    Life Sci.

    (1981)
  • S. Narumi et al.

    Thyrotrophin-releasing hormone (TRH) and its analog (DN-1417): Interaction with pentobarbital in choline uptake and acetylcholine synthesis of rat brain slices

    Life Sci.

    (1983)
  • J.M. Schaeffer et al.

    Regional differences in dopamine-mediated release of TRH-like material from synaptosomes

    Brain Res.

    (1977)
  • S. Yehuda et al.

    Peptides and thermo-regulation

    Neurosci. Biobehav. Rev.

    (1980)
  • G.W. Bennett et al.

    Concomitant determination of endogenous release of dopamine, noradrenaline, 5-hydroxytryptamine and thyrotrophin-releasing hormone (TRH) from rat brain slices and synaptosomes

  • G.W. Bennett et al.

    Analeptic effect of intracerebral injection of TRH and stabilized analogues in the pentobarbitone-anaesthetized rat

    Br. J. Pharmac.

    (1982)
  • Cited by (0)

    §

    Present address: Karolinska Institutet, Box 60 400, S-104 01 Stockholm 60 Sweden.

    Present address; Department of Pharmacology Ayerst Research Laboratories, 1025 Boulevard Laurentien, Saint Laurent, Montreal, Canada.

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