The effect of chronic CRF1 receptor blockade on the central CCK systems of Fawn-Hooded rats.
Corticotropin-releasing factor (CRF) is a neuropeptide associated with the integration of physiological and behavioural responses to stress. More recently, the CRF system has been implicated in the modulation of affective state and in the actions of abused drugs, including ethanol. As such, we have previously demonstrated that the selective, centrally acting CRF(1) receptor antagonist antalarmin displays an acute anxiolytic action and reduces established volitional ethanol consumption in isolation-reared Fawn-Hooded rats [Neuroscience 117 (2003) 243]. Similar to CRF, CCK is a neuropeptide found in high abundance throughout the neuraxis and is involved in the control of appetite, anxiety, reward and hormone regulation. Given the similar functions regulated by the neuropeptides CRF and CCK, it is of importance to determine whether interactions exist between these neuropeptides. Therefore, the aim of the present study was to examine the effects of chronic CRF(1) receptor blockade on the central CCK systems of Fawn-Hooded (FH) rats. Thus, bi-daily antalarmin treatment (20 mg/kg ip) induced a significant increase in CCK-B receptor-binding density throughout the neuraxis, indicative of either a global increase in receptor number or an increase in receptor affinity. In contrast, chronic antalarmin treatment resulted in bidirectional, region-specific changes in preproCCK messenger ribonucleic acid (mRNA) expression. Interestingly, this effect on CCK mRNA expression was restricted to the thalamocortico-limbic system, which is intimately involved in the integration of emotive behaviour and central reward processing. Therefore, these data provide clear evidence of the ability of chronic CRF(1) receptor blockade to significantly influence the central CCK systems of the rat.
Department of Pharmacology, Monash University, Box 13E, Clayton, Victoria 3800, Australia
Daniel J
DJ
Lodge
Andrew J
AJ
Lawrence
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D011743:Pyrimidines; D011758:Pyrroles; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D002766:Cholecystokinin; D003346:Corticotropin-Releasing Hormone