Selective breeding for increased cholinergic function: increased serotonergic sensitivity.

The effects of the serotonergic antagonist cyproheptadine and the agonist 1(m-chlorophenyl) piperazine (mCPP) on core body temperature, locomotor activity and operant responding for a water reward were determined in two lines of Sprague-Dawley rats selectively bred for differences in sensitivity to the anticholinesterase, diisopropyl fluorophosphate (DFP). Both cyproheptadine and mCPP induced a dose-dependent hypothermia that was significantly greater in the line of rat more sensitive to DFP (the Flinders Sensitive Line--FSL). On the other hand, the mild stimulant effects of cyproheptadine on operant responding and locomotor activity were similar in the two lines, whereas the marked inhibitory effects of mCPP on these two measures were significantly greater in the FSL rats. This study also confirmed that the FSL rats were significantly more sensitive to the hypothermic effects of oxotremorine, a muscarinic agonist, and showed that pretreatment with cyproheptadine reduced the hypothermic effects of oxotremorine to a similar extent in the two lines. These findings indicate that rats selectively bred for increased cholinergic function (FSL) also differ in their sensitivity to serotonergic agonists and antagonists, thereby extending the evidence for cholinergic-serotonergic interactions in the rat.