On the elevated plus-maze the anxiolytic-like effects of the 5-HT(1A) agonist, 8-OH-DPAT, but not the anxiogenic-like effects of the 5-HT(1A) partial agonist, buspirone, are blocked by the 5-HT1A antagonist, WAY 100635.
In the present study we evaluated the effects of the 5-HT(1A) receptor partial agonist, buspirone hydrochloride and the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on the elevated plus-maze. In addition, the ability of the 5-HT(1A) receptor antagonist, WAY 100635, to reverse the effects of both compounds was determined. 8-OH-DPAT (0.01 0.3 mg/kg, SC) dose-dependently increased the percent time on, and the number of entries to, the open arms of the maze. In a second experiment, WAY 100635 (0.003 0.3 mg/kg, SC) dose-dependently reversed the anxiolytic-like effects of 8-OH-DPAT (0.3 mg/kg, SC). In a third experiment, buspirone (0.3-4.0 mg/kg, SC) dose-dependently decreased the time spent on the open arms of the maze, indicating that it had anxiogenic-like effects. Buspirone also significantly decreased locomotor activity, which was evident in the decreases in the distance travelled on the open arms, closed arms and on the maze as a whole, the total number of arm entries and the mean speed of the animals. In contrast to its effects on 8-OH-DPAT-induced behaviours in the maze, WAY 100635 (0.003 1.0 mg/kg SC) failed to reverse any of the effects induced by buspirone. Animals treated with high doses of WAY 100635 (0.3 1.0 mg/kg SC) alone did not significantly differ from vehicle-treated animals on any of the measures recorded during elevated plus-maze trials. These data suggest that the anxiolytic-like effects of 8-OH-DPAT, but not the anxiogenic-like effects of buspirone, on the elevated plus-maze are mediated via 5-HT(1A) receptors in the CNS.
Collinson
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Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK.
Dawson
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GR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety; D002065:Buspirone / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents / Q000494:pharmacology*
D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone