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 drugs

High (+/-)-8-hydroxy-dipropylaminotetralin HBr (8-OH-DPAT) sensitive (HDS) rats and low 8-OH-DPAT-sensitive (LDS) rats were selectively bred for diffe rences in sensitivity to the hypothermic effect of the 5-hydroxytryptamine( 1A) (5-HT1A) 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 opera nt schedule. On this schedule, LDS rats had a higher response rate and a lo wer 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, desipram ine, decreased response rate and increased reinforcement rate of HDS and LD S rats, suggesting that norepinephrine function was similar in the two line s of rats. The finding with desipramine indicates that increases in reinfor cers on the differential reinforcement of low rate 72-s task are not simply dependent on baseline response or reinforcement rate. We also observed tha t 8-OH-DPAT engenders a greater hypothermic response in adult (90-day-old) HDS rats than in adult LDS rats. The 5-HT1A receptor antagonist WAY-100635 antagonized the hypothermic response. Tissue levels of 8-OH-DPAT from sever al brain regions in LDS and HDS rats did not differ from each other at eith er 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.