Low doses of 8-OH-DPAT prevent the impairment of spatial learning caused by intrahippocampal scopolamine through 5-HT(1A) receptors in the dorsal raphe.

1. We studied the effects of low doses of 8-OH-DPAT, a 5-HT(1A) receptor agonist, on the impairment of spatial learning caused by scopolamine injected into the CA1 region of the dorsal hippocampus of rats performing a two-platform spatial discrimination task. 2. Bilateral injections of 4 microg (in 1 microl) of scopolamine into the CA1 region of the dorsal hippocampus 10 min before each training session impaired choice accuracy with no effect on choice latency and errors of omission. 3. Administered subcutaneously 20 min before each training session, 8-OH-DPAT 10 and 30 (but not 3) microg kg(-1) did not modify choice accuracy but prevented the impairment by intrahippocampal scopolamine. 4. Injection of 1.0 microg (in 0.5 microl) of WAY 100635, a 5-HT(1A) receptor antagonist, into the dorsal raphe 5 min before scopolamine had no effect on choice accuracy and latency or errors of omission and did not modify the effect of scopolamine, but completely antagonized the effect of 10 and 30 microg kg(-1) 8-OH-DPAT on scopolamine-induced impairment of choice accuracy. 5. The results confirm previous findings that stimulation of presynaptic 5-HT(1A) receptors in the dorsal raphe attenuates the deficit of spatial learning caused by blockade of cholinergic excitatory input on hippocampal pyramidal cells. 6. Drugs that stimulate presynaptic 5-HT(1A) receptors such as 5-HT(1A) receptor partial agonists may be useful in the symptomatic treatment of human memory disturbances associated with loss of cholinergic innervation to the hippocampus.