Anxiolytic effects in the plus-maze of 5-HT1A-receptor ligands in dorsal raphe and ventral hippocampus

The response of rats naive to, or experienced with, the elevated plus-maze test of anxiety was observed following direct administration of the 5-HT1A-receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) (50, 100, or 200 ng) or antagonist tertatolol (3 mu g) into the dorsal raphe nucleus or bilaterally into the ventral hippocampus. In rats naive to the plus-maze, neither drug had a significant effect when microinjected into the dorsal raphe nucleus. However, in rats experienced with the plus-maze, 8-OH-DPAT (100 and 200 ng) had significant anxiolytic effects when administered to the dorsal raphe nucleus, which were antagonised by tertatolol (3 mu g); this suggests they were mediated by 5-HT1A receptors. Hyperactivity (increased number of closed-arm entries) was found following bilateral injection of 8-OH-DPAT (100 ng) into the ventral hippocampus of rats naive to the plus-maze. This was not completely antagonised by tertatolol (3 mu g). Interestingly, tertatolol (3 mu g) itself had an anxiolytic effect which was not antagonised by 8-OH-DPAT (100 ng), suggesting the effect was not mediated by 5-HT1A receptors, and indeed other actions of tertatolol, such as those on 5-HT1B or beta-adrenergic receptors could have been involved. In rats experienced with the plus-maze, tertatolol (3 mu g) again had a significant anxiolytic effect when administered bilaterally to the ventral hippocampus, and again, this was not antagonised by 8-OH-DPAT (100 ng). These results demonstrate that both the intracerebral location of the injection and test experience profoundly influence the effects of 5-HT1A ligands on behaviour of rats in the elevated plus-maze test of anxiety.