Vol. 292, Issue 1, 104-113, January 2000

Rats Selectively Bred for Responsiveness to 5-Hydroxytryptamine_1A Receptor Stimulation: Differences in Differential Reinforcement of Low Rate 72-Second Performance and Response to Serotonergic Drugs¹

Michael S. Cousins, Georgetta Vosmer, David H. Overstreet and Lewis S. Seiden

Departments of Pharmacological and Physiological Sciences, University of Chicago, Chicago, Illinois (M.S.C., G.V., L.S.S.); Center for Alcohol Studies and Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina (D.H.O.)

High (±)-8-hydroxy-dipropylaminotetralin HBr (8-OH-DPAT)-sensitive (HDS) rats and low 8-OH-DPAT-sensitive (LDS) rats were selectively bred for differences in sensitivity to the hypothermic effect of the 5-hydroxytryptamine_1A (5-HT_1A) receptor agonist 8-OH-DPAT in 30 to 35-day-old rat pups. These rats were trained on the differential reinforcement of low rate 72-s operant schedule. On this schedule, LDS rats had a higher response rate and a lower reinforcement rate than HDS rats. Drugs with primary action on the 5-HT system, 8-OH-DPAT, ketanserin, and fluoxetine, decreased response rate of HDS and LDS rats but increased the reinforcement rate of only the LDS rats. However, a drug with primary action on the norepinephrine system, desipramine, decreased response rate and increased reinforcement rate of HDS and LDS rats, suggesting that norepinephrine function was similar in the two lines of rats. The finding with desipramine indicates that increases in reinforcers on the differential reinforcement of low rate 72-s task are not simply dependent on baseline response or reinforcement rate. We also observed that 8-OH-DPAT engenders a greater hypothermic response in adult (90-day-old) HDS rats than in adult LDS rats. The 5-HT_1A receptor antagonist WAY-100635 antagonized the hypothermic response. Tissue levels of 8-OH-DPAT from several brain regions in LDS and HDS rats did not differ from each other at either 15- or 30-min postinjection. Because the LDS and HDS rats have different responses to 5-HT-acting drugs, these rats may be useful for studying the role of the serotonergic system in depression.