5-HT7 receptor stimulation by 8-OH-DPAT counteracts the impairing effect of 5-HT(1A) receptor stimulation on contextual learning in mice.

The principal 5-HT(1A) receptor agonist 8-Hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) impairs several different types of learning. Besides 5-HT(1A) receptors, 8-OH-DPAT stimulates 5-HT(7) receptors, but it is not known whether 5-HT(7) receptors contribute to the impairments. The 5-HT(7) receptor antagonist (2R)-1-[(3-Hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl] pyrrolidine (SB-269970) was combined with 8-OH-DPAT to dissociate 5-HT(1A) from 5-HT(7) receptor-mediated effects, in the passive avoidance task for emotional learning. SB-269970 intensified impairments caused by 8-OH-DPAT. SB-269970 alone had no effect on memory performance, but moderately decreased retention under suboptimal learning conditions. These findings indicate that 5-HT(7) receptor stimulation by 8-OH-DPAT counteracts 5-HT(1A) receptor-mediated impairments in hippocampal-dependent contextual learning.