Effects of 5-HT1A receptor ligands on a safety signal withdrawal procedure of conflict in the rat.
The present study evaluated in the rat the ability of various 5-HT1A receptor agonists to exert an "anxiolytic-like" release of the suppression of lever pressing for food induced by the withdrawal of a conditioned signal for safety without presentation of a conditioned signal for punishment. During the period associated with the safety signal withdrawal (Saf.CS-/Pun.CS-), control rats exhibited a typical pattern of responding with an initial strong blockade of responding that lessened over the period as presses were rewarded and shocks omitted. The 5-HT1A receptor partial agonists buspirone (0.125-0.5 mg/kg) and 8-(2-[2,3-dihydro-1,4-benzodioxin-2-yl- methylamino]ethyl)-8-azaspiro[4,5]decane-7,9-dione methyl sulfonate (MDL 73005EF; 0.5-2 mg/kg) and the full agonist (+)-4-[N-(5-methoxy-chroman-3-yl)-N-propylamino]-butyl-8- azaspiro[4,5]decane-7,9-dione (S 20499; 0.125-1 mg/kg) produced a robust and dose-related release of pressing during the Saf.CS-/Pun.CS- period. This effect was less marked with ipsapirone (0.125-1 mg/kg). Conversely, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.06-0.25 mg/kg), a full agonist, was completely inactive and did not prevent MDL 73005EF (1-2 mg/kg) or diazepam (0.125 mg/kg) from releasing the suppressed behavior. The specific 5-HT1A antagonist (+)-N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenylpr opa namide [(+)-WAY 100135; 0.25-8 mg/kg] and the beta-adrenoceptor/5-HT1A antagonist (-)-tertatolol (2-8 mg/kg) did not modify the behavioral blockade, nor did (+)-WAY 100135 (2-4 mg/kg) reduce the ability of buspirone (0.25 mg/kg) to enhance responding during the Saf.CS-/Pun.CS- period.(ABSTRACT TRUNCATED AT 250 WORDS)
Charrier
D
D
INSERM U-288, Paris, France.
Dangoumau
L
L
Hamon
M
M
Puech
A J
AJ
Thiébot
M H
MH
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004597:Electroshock; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects; D012055:Reinforcement Schedule; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects
D014151:Anti-Anxiety Agents; D008024:Ligands; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists