Antinociceptive tolerance revealed by cumulative intracranial microinjections of morphine into the periaqueductal gray in the rat

被引:60
作者
Morgan, Michael M. [1 ]
Fossum, Erin N. [1 ]
Levine, Carly S. [1 ]
Ingram, Susan L. [1 ]
机构
[1] Washington State Univ, Dept Psychol, Vancouver, WA 98686 USA
关键词
periaqueductal gray; rostral ventromedial medulla; analgesia; opioid; tolerance; pain;
D O I
10.1016/j.pbb.2006.08.003
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
The periaqueductal gray (PAG) appears to play a key role in morphine antinociception and tolerance. The objective of this manuscript is to develop a cumulative dose microinjection procedure so the hypothesized role of the PAG in morphine antinociceptive tolerance can be assessed using dose-response analysis. Rats were implanted with a guide cannula into the ventrolateral PAG. Microinjection of cumulative half log doses of morphine (0.32, 1, 3.2, and 10 mu g/0.4 mu l) produced antinociception on the hot plate test only at the two highest doses. Microinjection of quarter log doses of morphine into the PAG (1, 1.8, 3.2, 5.6, and 10 mu g/0.4 mu l) resulted in an ED50 for antinociception of 1.8 mu g. Systemic administration of the opioid antagonist naloxone increased the morphine ED50 to 9.0 mu g. Repeated microinjections of saline into the PAG had no effect on nociception. Pretreatment with twice daily injections of morphine, either systemically (5 mg/kg, s.c.) or into the PAG (5 mu g/0.4 mu l), for 2 days produced a two-fold increase in the ED50 for morphine antinociception. These data validate the use of an intracranial cumulative dose procedure to assess morphine potency and demonstrate that microinjection of morphine into the PAG is sufficient to produce tolerance. Published by Elsevier Inc.
引用
收藏
页码:214 / 219
页数:6
相关论文
共 27 条
[1]  
Chieng B, 1996, J NEUROSCI, V16, P7128
[2]   Antinociception produced by microinjection of morphine in the rat periaqueductal gray is enhanced in the foot, but not the tail, by intrathecal injection of α1-adrenoceptor antagonists [J].
Fang, F ;
Proudfit, HK .
BRAIN RESEARCH, 1998, 790 (1-2) :14-24
[3]   DEVELOPMENT OF TOLERANCE TO MORPHINE IN RAT [J].
FERNANDES, M ;
KLUWE, S ;
COPER, H .
PSYCHOPHARMACOLOGY, 1977, 54 (02) :197-201
[4]   DISINHIBITION OF OFF-CELLS AND ANTINOCICEPTION PRODUCED BY AN OPIOID ACTION WITHIN THE ROSTRAL VENTROMEDIAL MEDULLA [J].
HEINRICHER, MM ;
MORGAN, MM ;
TORTORICI, V ;
FIELDS, HL .
NEUROSCIENCE, 1994, 63 (01) :279-288
[5]  
Ingram SL, 1998, J NEUROSCI, V18, P10269
[6]   PERIAQUEDUCTAL GRAY - SITE OF MORPHINE ANALGESIA AND TOLERANCE AS SHOWN BY 2-WAY CROSS TOLERANCE BETWEEN SYSTEMIC AND INTRACEREBRAL INJECTIONS [J].
JACQUET, YF ;
LAJTHA, A .
BRAIN RESEARCH, 1976, 103 (03) :501-513
[7]   COMPARISON OF ANTINOCICEPTIVE ACTION OF MORPHINE IN THE PERIAQUEDUCTAL GRAY, MEDIAL AND PARAMEDIAL MEDULLA IN RAT .1. [J].
JENSEN, TS ;
YAKSH, TL .
BRAIN RESEARCH, 1986, 363 (01) :99-113
[8]   THE ANTINOCICEPTIVE ACTIVITY OF EXCITATORY AMINO-ACIDS IN THE RAT BRAIN-STEM - AN ANATOMICAL AND PHARMACOLOGICAL ANALYSIS [J].
JENSEN, TS ;
YAKSH, TL .
BRAIN RESEARCH, 1992, 569 (02) :255-267
[9]  
KALANT H, 1971, PHARMACOL REV, V23, P135
[10]   Morphine antinociception elicited from the ventrolateral periaqueductal gray is sensitive to sex and gonadectomy differences in rats [J].
Krzanowska, EK ;
Bodnar, RJ .
BRAIN RESEARCH, 1999, 821 (01) :224-230