Holtzman and Harlan Sprague-Dawley rats: differences in DRL 72-sec performance and 8-hydroxy-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 putative antidepressants; these compounds were evaluated in two outbred stocks of rats, Harlan and Holtzman Sprague-Dawley rats. A dose-response determination for the tricyclic antidepressants, imipramine and desipramine, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, fluoxetine, the 5-HT2 receptor antagonist, ketanserin, the 5-HT1A receptor agonist, (+/-)8-hydroxy-di-propylamino tetralin (8-OH-DPAT) and the dopamine releasing compound, amphetamine, were assessed in both rat stocks. The two stocks of rats differed in their baseline 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, fluoxetine and 8-OH-DPAT increased reinforcement rate and decreased response rate on the DRL 72-sec schedule, confirming previous studies. However, desipramine was the only drug to increase reinforcement rate and decrease response rate in both Holtzman and Harlan rats; in Harlan rats, drugs that primarily act upon the 5-HT system, imipramine, ketanserin, fluoxetine and 8-OH-DPAT, disrupted the DRL 72-sec performance and did not increase the number of reinforcements over baseline as was seen in Holtzman rats. Amphetamine disrupted DRL 72-sec performance in both Holtzman and Harlan rats in a similar manner. The hypothermic response to 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 mediated.
The University of Chicago, Department of Pharmacological and Physiological Sciences, Chicago, Illinois 60637, USA.
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013045:Species Specificity
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D018765:Dopamine Uptake Inhibitors; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors