CANNABINOID-INDUCED ANTINOCICEPTION IS MEDIATED BY A SPINAL ALPHA-2-NORADRENERGIC MECHANISM

被引:102
作者
LICHTMAN, AH [1 ]
MARTIN, BR [1 ]
机构
[1] VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL, BOX 613,MCV STN, RICHMOND, VA 23298 USA
关键词
DELTA-9-TETRAHYDROCANNABINOL; YOHIMBINE; METHYSERGIDE; ANTINOCICEPTION; CATALEPSY; HYPOTHERMIA;
D O I
10.1016/0006-8993(91)90017-P
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The present study examined whether descending noradrenergic and serotonergic systems mediate the antinociceptive effect of the prototypical cannabinoid, delta-9-tetrahydrocannabinol (DELTA-9-THC). Rats were administered vehicle or DELTA-9-THC (10 mg/kg, i.v.) and subsequently given an intrathecal (i.t.) injection of either the alpha-2-noradrenergic antagonist, yohimbine, or the non-specific serotonin (5-HT) antagonist, methysergide, through chronically implanted spinal catheters. Whereas yohimbine significantly reversed the cannabinoid-induced elevation of tail-flick latencies, methysergide had no effect. To examine whether yohimbine was indeed blocking the antinociceptive effects of DELTA-9-THC through a spinal mechanism, it was administered i.t. at either the lumbar or the upper thoracic level of the spinal cord. Antinociception was significantly reduced when yohimbine was administered in the lumbar region; however, administration in the upper thoracic region failed to have an effect. In addition, the effect of i.t. administered yohimbine and methysergide was assessed on two other indices sensitive to cannabinoids, hypothermia and ring immobility. As previously reported, i.v. administration of DELTA-9-THC led to hypothermia as well as immobility in the ring test which were not blocked by i.t. administration of either monoamine antagonist. To the contrary, methysergide potentiated the hypothermic effect of DELTA-9-THE. These findings indicate that cannabinoids activate descending noradrenergic neurons resulting in antinociception via the stimulation of spinal alpha-2-adrenoceptors.
引用
收藏
页码:309 / 314
页数:6
相关论文
共 41 条
[1]   EFFECTS OF INTRATHECALLY ADMINISTERED METHYSERGIDE AND YOHIMBINE ON MICROSTIMULATION-PRODUCED ANTINOCICEPTION IN THE RAT [J].
BARBARO, NM ;
HAMMOND, DL ;
FIELDS, HL .
BRAIN RESEARCH, 1985, 343 (02) :223-229
[2]   BILATERAL INTRANIGRAL MICROINJECTION OF MORPHINE AND OPIOID-PEPTIDES PRODUCES ANTINOCICEPTION IN RATS [J].
BAUMEISTER, AA ;
HAWKINS, MF ;
ANTICICH, TG ;
MOORE, LL ;
HIGGINS, TD .
BRAIN RESEARCH, 1987, 411 (01) :183-186
[3]   EVIDENCE THAT THE SUBSTANTIA NIGRA IS A COMPONENT OF THE ENDOGENOUS PAIN SUPPRESSION SYSTEM IN THE RAT [J].
BAUMEISTER, AA ;
ANTICICH, TG ;
HAWKINS, MF ;
LITER, JC ;
THIBODEAUX, HF ;
GUILLORY, EC .
BRAIN RESEARCH, 1988, 447 (01) :116-121
[4]   ANTINOCICEPTION INDUCED BY LOCAL INJECTIONS OF CARBACHOL INTO THE NUCLEUS RAPHE MAGNUS IN RATS - ALTERATION BY INTRATHECAL INJECTION OF MONOAMINERGIC ANTAGONISTS [J].
BRODIE, MS ;
PROUDFIT, HK .
BRAIN RESEARCH, 1986, 371 (01) :70-79
[5]  
D'amour FE, 1941, J PHARMACOL EXP THER, V72, P74
[6]  
DEVANE WA, 1988, MOL PHARMACOL, V34, P605
[7]  
DEWEY WL, 1970, J PHARMACOL EXP THER, V175, P435
[8]  
DEWEY WL, 1986, PHARMACOL REV, V38, P151
[9]   ELECTRICAL-STIMULATION OF THE SUBSTANTIA NIGRA DOES NOT INCREASE TAIL-FLICK LATENCY IN THE RAT [J].
DUGGAL, KN ;
BARASI, S .
EXPERIMENTAL NEUROLOGY, 1985, 87 (02) :300-308
[10]   INVESTIGATIONS ON BEHAVIORAL-EFFECTS OF AN EXTRACT OF CANNABIS-SATIVA L IN THE RAT [J].
FERRI, S ;
COSTA, G ;
MURARI, G ;
PANICO, AM ;
RAPISARDA, E ;
SPERONI, E ;
ARRIGOREINA, R .
PSYCHOPHARMACOLOGY, 1981, 75 (02) :144-147