Stimulation of 5-HT1A receptors in the dorsal raphe reverses the impairment of spatial learning caused by intrahippocampal scopolamine in rats.
This study investigated the effect of stimulating 5-HT1A receptors in the dorsal raphe on the impairment of learning caused by 4 microg/microL scopolamine injected in the CA1 region of the dorsal hippocampus in rats performing a two-platform spatial discrimination task. At 1 (but not 0.2) microg/0.5 microL administered in the dorsal raphe on each acquisition training day 5 min before bilateral intrahippocampal injection of 4 microg/microL scopolamine, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, had no effect on choice accuracy and latency or errors of omission but completely antagonized the impairment of choice accuracy by intrahippocampal scopolamine. Administered into the dorsal raphe at 0.2 and 1 microg/0.5 microL, WAY 100635, a 5-HT1A receptor antagonist, had no effect on rats' performance or on the impairment caused by intrahippocampal scopolamine but dose-dependently antagonized the effect of 1 microg/0.5 microL 8-OH-DPAT on the scopolamine-induced deficit. The results show that stimulation of presynaptic 5-HT1A receptors in the dorsal raphe reverses the deficit caused by intrahippocampal scopolamine, probably by facilitating the transfer of facilitatory information from the entorhinal cortex to the hippocampus. Together with a previous study showing that blockade of postsynaptic hippocampal 5-HT1A receptors antagonized the effect of intrahippocampal scopolamine in the two-platform spatial discrimination task (Carli et al., 1995b), the results suggest that drugs with presynaptic stimulatory and postsynaptic blocking actions on 5-HT1A receptors, such as partial agonists at these receptors, may be useful in the symptomatic treatment of human memory disturbances associated with loss of cholinergic innervation to the hippocampus.
Carli
M
M
Laboratory of Neuropharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Bonalumi
P
P
Samanin
R
R
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000737:chemistry*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012601:Scopolamine / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology
D018727:Muscarinic Antagonists; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012601:Scopolamine