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-phenylpropanamide [(+)-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. Finally, neither 1-(2-pyrimidinyl)piperazine (1-PP), the common metabolite of azapirones, with alpha(2)-adrenoceptor antagonist properties, nor the D-2-receptor antagonist l-sulpiride reduced the behavioral suppression. These data suggest that the activation of somatodendritic and/or postsynaptic 5-HT1A receptors does not entirely account for the anxiolytic-like effects of 5-HT1A agonists in this procedure of conflict in the rat.