Antidepressant-like effects of CCKB receptor antagonists: Involvement of the opioid system

被引:19
作者
Hernando, F
Fuentes, JA
FournieZaluski, MC
Roques, BP
RuizGayo, M
机构
[1] UNIV COMPLUTENSE MADRID,FAC FARM,DEPT FARMACOL,E-28040 MADRID,SPAIN
[2] UFR SCI PHARMACEUT & BIOL,URA D1500 CNRS,U266 INSERM,DEPT PHARMACOCHIM MOL & STRUCT,F-75270 PARIS 06,FRANCE
关键词
cholecystokinin; CCK-8; BC; 264; CCKB receptor antagonist; L-365,260; devazepide; CCKA receptor antagonist; depression; stress; forced-swimming test; RB; 101; enkephalin catabolism inhibitor;
D O I
10.1016/S0014-2999(96)00773-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
RE 101 (N-[(R, S)-2-benzyl-3-[(S)-2-amino-4-methylthiobutyldithio]-1-oxopropyl]-L-phenylalaninebenzyl ester), a systemically active inhibitor of enkephalin catabolism, has been shown to elicit antidepressant-like effects in mice, both in the forced-swimming and in the conditioned suppression of the mobility tests. The same type of response has been also observed following administration of the cholecystokinin CCKB receptor antagonist L-365,260 ((3R)-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-3-methylphenylurea). Interestingly, the delta-opioid receptor antagonist naltrindole (17-cyclopropylmethyl-6,7-dehydro-4,5 alpha-epoxy-3,14-dihydroxy-6,7,2'-3'-indolomorphinan) blocks the effect of both RE 101 and L-365,260 in the conditioned suppression of the motility test. In this work we have investigated the involvement of the opioid system in the antidepressant response to the CCKB receptor antagonist L-365,260 in the forced-swimming test in mice. The effect of L-365,260 was decreased by the delta-opioid receptor antagonist naltrindole. Furthermore, the CCKB receptor agonist, BC 264 (Boc-Tyr(OSO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2), blocked the antidepressant-like effect of RE 101 while CCK-8 (H-Asp-Tyr(OSO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2) enhanced the effect of this drug, probably through stimulation of central CCKA receptors, since the CCKA receptor antagonist devazepide ((3S)-(-)-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-1H-indole-2-carboxamide) abolished the CCK-8-induced potentiation of the RE 101 effect. In addition, RE 101 enhanced the effect of L-365,260. Such an effect was blocked by the delta-opioid receptor antagonist naltrindole. These data further support the involvement of opioid receptors in the antidepressant-type effect induced by CCKB receptor blockers and support the hypothesis of a regulatory role of CCK in the activity of the endogenous opioid system. As in other experimental paradigms, CCKA and CCKB receptor stimulation appears to have opposite effects in modulating opioidergic activity.
引用
收藏
页码:221 / 229
页数:9
相关论文
共 69 条
[1]  
[Anonymous], OPIATES ENDOGENOUS O
[2]  
[Anonymous], CHOLECYSTOKININ ANXI
[3]   INCREASE IN RAT CORTICAL [H-3] NALOXONE BINDING-SITE DENSITY AFTER CHRONIC ADMINISTRATION OF ANTIDEPRESSANT AGENTS [J].
ANTKIEWICZMICHALUK, L ;
ROKOSZPELC, A ;
VETULANI, J .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1984, 102 (01) :179-181
[4]  
BAAMONDE A, 1991, J PHARMACOL EXP THER, V257, P767
[5]   ANTIDEPRESSANT-TYPE EFFECTS OF ENDOGENOUS ENKEPHALINS PROTECTED BY SYSTEMIC RB-101 ARE MEDIATED BY OPIOID-DELTA AND DOPAMINE-D1 RECEPTOR STIMULATION [J].
BAAMONDE, A ;
DAUGE, V ;
RUIZGAYO, M ;
FULGA, IG ;
TURCAUD, S ;
FOURNIEZALUSKI, MC ;
ROQUES, BP .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1992, 216 (02) :157-166
[6]   THE ROLE OF CCK, CERULEIN, AND CCK ANTAGONISTS IN NOCICEPTION [J].
BABER, NS ;
DOURISH, CT ;
HILL, DR .
PAIN, 1989, 39 (03) :307-328
[7]   INVOLVEMENT OF ENDOGENOUS ENKEPHALINS IN THE MOUSE BEHAVIORAL DESPAIR TEST [J].
BENNATAN, L ;
CHAILLET, P ;
LECOMTE, JM ;
MARCAIS, H ;
UCHIDA, G ;
COSTENTIN, J .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1984, 97 (3-4) :301-304
[8]   OPIOID CONTROL OF THE INVITRO RELEASE OF CHOLECYSTOKININ-LIKE MATERIAL FROM THE RAT SUBSTANTIA-NIGRA [J].
BENOLIEL, JJ ;
MAUBORGNE, A ;
BOURGOIN, S ;
LEGRAND, JC ;
HAMON, M ;
CESSELIN, F .
JOURNAL OF NEUROCHEMISTRY, 1992, 58 (03) :916-922
[9]   DIFFERENTIAL INHIBITORY STIMULATORY MODULATION OF SPINAL CCK RELEASE BY MU-OPIOID AND DELTA-OPIOID AGONISTS, AND SELECTIVE BLOCKADE OF MU-DEPENDENT INHIBITION BY KAPPA-RECEPTOR STIMULATION [J].
BENOLIEL, JJ ;
BOURGOIN, S ;
MAUBORGNE, A ;
LEGRAND, JC ;
HAMON, M ;
CESSELIN, F .
NEUROSCIENCE LETTERS, 1991, 124 (02) :204-207
[10]   AMPHETAMINE, COCAINE, PHENCYCLIDINE AND NOMIFENSINE INCREASE EXTRACELLULAR DOPAMINE CONCENTRATIONS PREFERENTIALLY IN THE NUCLEUS ACCUMBENS OF FREELY MOVING RATS [J].
CARBONI, E ;
IMPERATO, A ;
PEREZZANI, L ;
DICHIARA, G .
NEUROSCIENCE, 1989, 28 (03) :653-661