Corticotropin-releasing factor decreases meal size by decreasing cluster number in Koletsky (LA/N) rats with and without a null mutation of the leptin receptor

The homozygous mutant Koletsky rat is a monogenic form of obesity and hyperphagia due to a null mutation of the leptin receptor (lepr(fak)). To investigate if the lack of leptin action on the brain of homozygous mutants affected the inhibitory potency of corticotropin-releasing factor (CRF) on meal size, artificial cerebrospinal fluid or one of five doses of CRF was administered through third ventricular cannulas in 8 +/+, 10 +/fa(k), and 8 fa(k)/fa(k) rats 15 min before access to 20% sucrose in lickometer tubes for 30 min. CRF had equivalent inhibitory potency in fa(k)/fa(k) and +/+ rats. Thus, the complete lack of leptin action in fa(k)/fa(k) rats did not change the inhibitory potency of CRF. CRF was significantly more potent, however, in +/fa(k) rats than in the other two genotypes. Thus, the heterozygote condition of this mutation did not function as a classical recessive mutation for this behavioral phenotype. Despite these differences in potency, microstructural analysis revealed that CRF decreased intakes in all three genotypes by decreasing the number of clusters of licking without changing the size of clusters.