The CRF1 receptor antagonist antalarmin reduces volitional ethanol consumption in isolation-reared fawn-hooded rats.
Corticotropin releasing factor is a neuropeptide associated with the integration of physiological and behavioural responses to stress. More recently, corticotropin releasing factor has been implicated in the actions of abused drugs, including ethanol. Moreover, previous studies have demonstrated that the non-selective corticotropin releasing factor receptor antagonist, alpha-helical corticotropin releasing factor(9-41), can diminish some of the behavioural effects associated with ethanol withdrawal, whilst the selective corticotropin releasing factor(1) receptor antagonist CP-154,526 has been beneficial in decreasing stress-induced relapse into alcohol-seeking behaviour. However, as yet the ability of selective corticotropin releasing factor compounds to modulate volitional ethanol consumption has not been investigated. For these reasons the present study aims to examine the effects of antalarmin, a selective, centrally acting corticotropin releasing factor(1) receptor antagonist, on both the initiation and maintenance of ethanol consumption in isolation-reared Fawn-Hooded rats. Here we demonstrate that whilst both antalarmin and diazepam can decrease the acquisition of an ethanol-preferring phenotype by Fawn-Hooded rats, only antalarmin can alter established, volitional ethanol consumption. This ability of antalarmin to reduce established ethanol consumption is apparently unrelated to changes in ingestive behaviour, or a generalised anxiolytic action. For these reasons, such drugs may provide a new therapeutic approach for the treatment of alcoholism; however, this requires further investigation.
Lodge
D J
DJ
Department of Pharmacology, Monash University, Box 13E, Clayton, Victoria 3800, Australia. daniel.lodge@med.monash.edu.au
Lawrence
A J
AJ
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology; D012934:Social Isolation / Q000523:psychology; D014836:Volition / Q000187:drug effects* / Q000502:physiology; D000099052:CRF Receptor, Type 1
D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D000099052:CRF Receptor, Type 1