Substance P(1-7) affects the expression of dopamine D2 receptor mRNA in male rat brain during morphine withdrawal.
Previous studies have confirmed an important role of the undecapeptide substance P (SP) in opioid reward and dependence. It is further shown that the SP N-terminal metabolite SP(1-7) may attenuate the intensity of opioid withdrawal in mice. In this study we have investigated the effect of the heptapeptide fragment on the expression of the brain dopamine D2 receptor mRNA and on the withdrawal reaction, as well, in morphine-dependent rats. Male Sprague-Dawley rats were randomly distributed into two groups. Guide cannula was implanted and aimed at the lateral ventricle and animals were subsequently made opioid dependent by two daily injections of morphine (10 mg/kg) for 7 days. Half an hour before naloxone challenge (2 mg/kg) one group of rats received an injection of SP(1-7) (28 nmol per rat) and the other, serving as control, was injected with saline through the cannula. Animals were decapitated 4 h following SP(1-7) or saline injections. The results indicated that the level of the dopamine D2 receptor transcript was significantly reduced by SP(1-7) in nucleus accumbens and frontal cortex but not altered in the striatum. In behavioral tests it was found that the heptapeptide attenuated several somatic withdrawal symptoms. The observed reduction in the receptor transcript in nucleus accumbens and frontal cortex is suggested to reflect an increased dopamine activity in these areas, which in turn may counteract the withdrawal reaction.
Zhou
Qin
Q
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, PO Box 591, S-751 24 Uppsala, Sweden.
Frändberg
Per-Anders
PA
Kindlundh
Anna M S
AM
Le Grevès
Pierre
P
Nyberg
Fred
F
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D013373:Substance P / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000235:genetics*
D010446:Peptide Fragments; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D013373:Substance P; C036877:substance P (1-7); D009020:Morphine