Benzodiazepine withdrawal facilitates the subsequent onset of escape failures and anhedonia: influence of different antidepressant drugs

LACERRA C, MARTIJENA ID, BUSTOS SG, MOLINA VA

BRAIN RESEARCH

ELSEVIER SCIENCE BV

Año: 1999 p. 40 - 47

0006-8993

Abstract The effect of benzodiazepine BDZ. withdrawal on escape acquisition and on the behavioral response to two different reinforcing stimuli was investigated. In addition, the influence of antidepressant drugs AD. differing in their mechanism of action on these behavioral outputs was also evaluated. Rats subjected to withdrawal from a chronic treatment with diazepam DZM; 2 mgrkg per day, i.p.. during 21 days were subsequently exposed to a brief inescapable shock session IS. and 48 h later to an active avoidance test. Only withdrawn animals exposed to the IS exhibited enhanced escape failures. In an additional experiment, withdrawn rats were repeatedly administered with vehicle VEH., desipramine DMI; 5 mgrkg, i.p.., fluoxetine FLU; 5 mgrkg, i.p.. or phenelzine PHEN; 5 mgrkg, i.p.. and subsequently exposed to IS and to active avoidance task. A significant reversal of escape deficit was only observed following DMI and PHEN but not after FLU. Furthermore, withdrawn rats showed a reduced preference for a sexually relevant olfactory cue, this reduced sensitivity was only normalized following DMI but not after the administration of FLU or PHEN. Finally, rats exposed to abrupt cessation of chronic BDZ administration did not exhibit preference for a context previously associated with amphetamine AMP. under the conditioned place preference CPP. procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes—escape failures and reduced behavioral response to rewarding stimuli—suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake. q1999 Published by ELsevier Science B.V. All rights reserved.BDZ. withdrawal on escape acquisition and on the behavioral response to two different reinforcing stimuli was investigated. In addition, the influence of antidepressant drugs AD. differing in their mechanism of action on these behavioral outputs was also evaluated. Rats subjected to withdrawal from a chronic treatment with diazepam DZM; 2 mgrkg per day, i.p.. during 21 days were subsequently exposed to a brief inescapable shock session IS. and 48 h later to an active avoidance test. Only withdrawn animals exposed to the IS exhibited enhanced escape failures. In an additional experiment, withdrawn rats were repeatedly administered with vehicle VEH., desipramine DMI; 5 mgrkg, i.p.., fluoxetine FLU; 5 mgrkg, i.p.. or phenelzine PHEN; 5 mgrkg, i.p.. and subsequently exposed to IS and to active avoidance task. A significant reversal of escape deficit was only observed following DMI and PHEN but not after FLU. Furthermore, withdrawn rats showed a reduced preference for a sexually relevant olfactory cue, this reduced sensitivity was only normalized following DMI but not after the administration of FLU or PHEN. Finally, rats exposed to abrupt cessation of chronic BDZ administration did not exhibit preference for a context previously associated with amphetamine AMP. under the conditioned place preference CPP. procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes—escape failures and reduced behavioral response to rewarding stimuli—suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake. q1999 Published by ELsevier Science B.V. All rights reserved.AD. differing in their mechanism of action on these behavioral outputs was also evaluated. Rats subjected to withdrawal from a chronic treatment with diazepam DZM; 2 mgrkg per day, i.p.. during 21 days were subsequently exposed to a brief inescapable shock session IS. and 48 h later to an active avoidance test. Only withdrawn animals exposed to the IS exhibited enhanced escape failures. In an additional experiment, withdrawn rats were repeatedly administered with vehicle VEH., desipramine DMI; 5 mgrkg, i.p.., fluoxetine FLU; 5 mgrkg, i.p.. or phenelzine PHEN; 5 mgrkg, i.p.. and subsequently exposed to IS and to active avoidance task. A significant reversal of escape deficit was only observed following DMI and PHEN but not after FLU. Furthermore, withdrawn rats showed a reduced preference for a sexually relevant olfactory cue, this reduced sensitivity was only normalized following DMI but not after the administration of FLU or PHEN. Finally, rats exposed to abrupt cessation of chronic BDZ administration did not exhibit preference for a context previously associated with amphetamine AMP. under the conditioned place preference CPP. procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes—escape failures and reduced behavioral response to rewarding stimuli—suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake. q1999 Published by ELsevier Science B.V. All rights reserved.DZM; 2 mgrkg per day, i.p.. during 21 days were subsequently exposed to a brief inescapable shock session IS. and 48 h later to an active avoidance test. Only withdrawn animals exposed to the IS exhibited enhanced escape failures. In an additional experiment, withdrawn rats were repeatedly administered with vehicle VEH., desipramine DMI; 5 mgrkg, i.p.., fluoxetine FLU; 5 mgrkg, i.p.. or phenelzine PHEN; 5 mgrkg, i.p.. and subsequently exposed to IS and to active avoidance task. A significant reversal of escape deficit was only observed following DMI and PHEN but not after FLU. Furthermore, withdrawn rats showed a reduced preference for a sexually relevant olfactory cue, this reduced sensitivity was only normalized following DMI but not after the administration of FLU or PHEN. Finally, rats exposed to abrupt cessation of chronic BDZ administration did not exhibit preference for a context previously associated with amphetamine AMP. under the conditioned place preference CPP. procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes—escape failures and reduced behavioral response to rewarding stimuli—suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake. q1999 Published by ELsevier Science B.V. All rights reserved.. during 21 days were subsequently exposed to a brief inescapable shock session IS. and 48 h later to an active avoidance test. Only withdrawn animals exposed to the IS exhibited enhanced escape failures. In an additional experiment, withdrawn rats were repeatedly administered with vehicle VEH., desipramine DMI; 5 mgrkg, i.p.., fluoxetine FLU; 5 mgrkg, i.p.. or phenelzine PHEN; 5 mgrkg, i.p.. and subsequently exposed to IS and to active avoidance task. A significant reversal of escape deficit was only observed following DMI and PHEN but not after FLU. Furthermore, withdrawn rats showed a reduced preference for a sexually relevant olfactory cue, this reduced sensitivity was only normalized following DMI but not after the administration of FLU or PHEN. Finally, rats exposed to abrupt cessation of chronic BDZ administration did not exhibit preference for a context previously associated with amphetamine AMP. under the conditioned place preference CPP. procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes—escape failures and reduced behavioral response to rewarding stimuli—suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake. q1999 Published by ELsevier Science B.V. All rights reserved.VEH., desipramine DMI; 5 mgrkg, i.p.., fluoxetine FLU; 5 mgrkg, i.p.. or phenelzine PHEN; 5 mgrkg, i.p.. and subsequently exposed to IS and to active avoidance task. A significant reversal of escape deficit was only observed following DMI and PHEN but not after FLU. Furthermore, withdrawn rats showed a reduced preference for a sexually relevant olfactory cue, this reduced sensitivity was only normalized following DMI but not after the administration of FLU or PHEN. Finally, rats exposed to abrupt cessation of chronic BDZ administration did not exhibit preference for a context previously associated with amphetamine AMP. under the conditioned place preference CPP. procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes—escape failures and reduced behavioral response to rewarding stimuli—suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake. q1999 Published by ELsevier Science B.V. All rights reserved.. and subsequently exposed to IS and to active avoidance task. A significant reversal of escape deficit was only observed following DMI and PHEN but not after FLU. Furthermore, withdrawn rats showed a reduced preference for a sexually relevant olfactory cue, this reduced sensitivity was only normalized following DMI but not after the administration of FLU or PHEN. Finally, rats exposed to abrupt cessation of chronic BDZ administration did not exhibit preference for a context previously associated with amphetamine AMP. under the conditioned place preference CPP. procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes—escape failures and reduced behavioral response to rewarding stimuli—suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake. q1999 Published by ELsevier Science B.V. All rights reserved.AMP. under the conditioned place preference CPP. procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes—escape failures and reduced behavioral response to rewarding stimuli—suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake. q1999 Published by ELsevier Science B.V. All rights reserved.CPP. procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes—escape failures and reduced behavioral response to rewarding stimuli—suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake. q1999 Published by ELsevier Science B.V. All rights reserved.q1999 Published by ELsevier Science B.V. All rights reserved.