Involvement of protein kinase Cγ isoform in morphine-induced reinforcing effects
Section snippets
Experimental procedures
The present study was conducted in accordance with the Guiding Principles for the Care and Use of Laboratory Animals, Hoshi University, as adopted by the Committee on Animal Research of Hoshi University, which is accredited by the Ministry of Education, Science, Sports and Culture of Japan. Every effort was made to minimize the numbers and any suffering of animals used in the experiments.
Role of protein kinase C in the morphine-induced reinforcing effect
The saline-control mice exhibited no preference for either place: the mean conditioning score was −27.6±41.7 s. As shown in Fig. 1A, morphine (1–5 mg/kg, s.c.) produced a significant dose-dependent preference for the drug-associated place (F3,28=2.95, P<0.05). An i.c.v. treatment with the vehicle also produced no preference for either place: the mean conditioning score was −42.3±35.7 s. The selective PKC inhibitor calphostin C (10–100 pmol/mouse, i.c.v.) alone induced neither significant place
Discussion
Although it is well known that morphine acts primarily on the μ-opioid receptors, the effects of morphine on signaling elements are modulated through its receptors in opioid addiction.22., 23., 26. Chronic adaptive molecular mechanisms in opioid addiction may be involved in some protein kinases (e.g. PKC, protein kinase A and G-protein-coupled receptor kinase).
The PKCs are a family of phospholipid-dependent serine/threonine protein kinases that are highly concentrated in the brain.7 PKC plays a
Conclusions
The present behavioral studies provide direct evidence for the involvement of PKCγ in the morphine-induced place preference in mice. This contention is further supported by the present biochemical finding of the up-regulation of PKCγ, but not PKCα, βI, βII or ε, isoforms in the limbic forebrain of mice in the morphine-conditioning schedule. Thus, we propose here that the concomitant activation of the PKCγ isoform in the limbic forebrain by morphine may contribute to the induction of the
Acknowledgements
This work was supported in part by grants from the Ministry of Health and Welfare, and the Ministry of Education, Science, Sports and Culture of Japan to T. Suzuki.
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