A comparison of the motor behaviours produced by the intrathecal administration of thyrotrophin-releasing hormone and thyrotrophin-releasing hormone analogues in the conscious rat.
The behaviours evoked by the intrathecal injection of thyrotrophin-releasing hormone and a variety of analogues (RX77368, CG3509 and CG3703) were examined in conscious rats and the spread of injectate at the peak of the behavioural response was determined using 14C-labelled RX77368. The number of wet-dog shakes observed following intrathecal injection of thyrotrophin-releasing hormone, RX77368, CG3509 and CG3703 was linearly related to log10 dose (0.01-200 micrograms) in the first 6 min with the relative potencies being 1:7:10:60 respectively. The thyrotrophin-releasing hormone analogues also produced a marked forepaw-licking behaviour, but this did not increase with dose. Intrathecal or intraperitoneal pretreatment with prazosin (0.5 microgram and 1 or 2 mg/kg, respectively) attenuated both the wet-dog shake and forepaw-licking behaviours normally produced by the thyrotrophin-releasing hormone peptides. Following intrathecal [14C]RX77368 the radioactivity was principally restricted to the spinal cord with only limited amounts rostral to the rhombencephalon. These results imply that a tonically active bulbospinal noradrenergic pathway facilitates both thyrotrophin-releasing hormone-induced behaviours via alpha 1-adrenoceptors.
Johnson
J V
JV
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Fone
K C
KC
Havler
M E
ME
Tulloch
I F
IF
Bennett
G W
GW
Marsden
C A
CA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*
C036430:orotirelin; C031926:montirelin; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D011761:Pyrrolidonecarboxylic Acid; D011224:Prazosin