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 r eceptor agonists to exert an ''anxiolytic-like'' release of the suppre ssion of lever pressing for food induced by the withdrawal of a condit ioned signal for safety without presentation of a conditioned signal f or punishment. During the period associated with the safety signal wit hdrawal (Saf.CS-/Pun.CS-), control rats exhibited a typical pattern of responding with an initial strong blockade of responding that lessene d over the period as presses were rewarded and shocks omitted. The 5-H T1A receptor partial agonists buspirone (0.125-0.5 mg/kg) and methylam inoethyl)-8-azaspiro4,5decane-7,9-dione methyl sulfonate (MDL 73005 EF; 0.5-2 mg/kg) and the full agonist propylamino-butyl-8-azaspiro4, 5decane-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 e ffect was less marked with ipsapirone (0.125-1 mg/kg). Conversely, 8-h ydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.06-0.25 mg/kg), a fu ll agonist, was completely inactive and did not prevent MDL 73005EF (1 -2 mg/kg) or diazepam (0.125 mg/kg) from releasing the suppressed beha vior. The specific 5-HT1A antagonist 2-methoxyphenyl)piperazin-1-yl-2- phenylpropanamide (+)-WAY 100135; 0.25-8 mg/kg and the beta-adrenoce ptor/5-HT1A antagonist (-)-tertatolol (2-8 mg/kg) did not modify the b ehavioral blockade, nor did (+)-WAY 100135 (2-4 mg/kg) reduce the abil ity of buspirone (0.25 mg/kg) to enhance responding during the Saf.CS- /Pun.CS period. Finally, neither 1-(2-pyrimidinyl)piperazine (1-PP), t he common metabolite of azapirones, with alpha(2)-adrenoceptor antagon ist properties, nor the D-2-receptor antagonist l-sulpiride reduced th e behavioral suppression. These data suggest that the activation of so matodendritic and/or postsynaptic 5-HT1A receptors does not entirely a ccount for the anxiolytic-like effects of 5-HT1A agonists in this proc edure of conflict in the rat.