Anxiolytic effects in the plus-maze of 5-HT1A-receptor ligands in dorsal raphé 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 micrograms) into the dorsal raphé 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 raphé 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 raphé nucleus, which were antagonised by tertatolol (3 micrograms); 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 micrograms). Interestingly, tertatolol (3 micrograms) 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 micrograms) 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.
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Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London, UK. s.file@umds.ac.uk
Gonzalez
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008024:Ligands; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013238:Stereotaxic Techniques; D013876:Thiophenes
D000319:Adrenergic beta-Antagonists; D014151:Anti-Anxiety Agents; D008024:Ligands; D011412:Propanolamines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D013876:Thiophenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C005632:tertatolol