HOLTZMAN AND HARLAN SPRAGUE-DAWLEY RATS - DIFFERENCES IN DRL 72-SEC PERFORMANCE AND 8-HYDROXY-INDUCED DI-PROPYLAMINO TETRALIN-INDUCED HYPOTHERMIA

Several compounds were tested on the differential-reinforcement-of-low -rate 72-sec (DRL 72-sec) schedule, a behavioral screen to determine p utative antidepressants; these compounds were evaluated in two outbred stocks of rats, Harlan and Holtzman Sprague-Dawley rats. A dose-respo nse determination for the tricyclic antidepressants, imipramine and de sipramine, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptak e inhibitor, fluoxetine, the 5-HT2 receptor antagonist, ketanserin, th e 5-HT1A receptor agonist, (+/-)8-hydroxy-di-propylamino tetralin (8-O H-DPAT) and the dopamine releasing compound, amphetamine, were assesse d in both rat stocks. The two stocks of rats differed in their baselin e performance on the DRL 72-sec schedule. The Harlan rats had a higher reinforcement rate and a lower response rate than the Holtzman rats. In Holtzman, but not in Harlan rats, imipramine, ketanserin, fluoxetin e and 8-OH-DPAT increased reinforcement rate and decreased response ra te on the DRL 72-sec schedule, confirming previous studies. However, d esipramine was the only drug to increase reinforcement rate and decrea se response rate in both Holtzman and Harlan rats; in Harlan rats, dru gs that primarily act upon the 5-HT system, imipramine, ketanserin, fl uoxetine and 8-OH-DPAT, disrupted the DRL 72-sec performance and did n ot increase the number of reinforcements over baseline as was seen in Holtzman rats. Amphetamine disrupted DRL 72-sec performance in both Ho ltzman and Harlan rats in a similar manner. The hypothermic response t o 8-OH-DPAT was also assessed in the two stocks of rats; Holtzman rats had a smaller decrease in core body temperature than Harlan rats. The observed behavioral and pharmacological differences between Holtzman and Harlan rat stocks may be genetically and/or environmentally mediat ed.