Open AccessIncreased response to morphine in mice lacking protein kinase C epsilon
Author(s) -
Newton P. M.,
Kim J. A.,
McGeehan A. J.,
Paredes J. P.,
Chu K.,
Wallace M. J.,
Roberts A. J.,
Hodge C. W.,
Messing R. O.
Publication year - 2007
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2006.00261.x
Subject(s) - morphine , protein kinase c , opiate , conditioned place preference , pharmacology , kinase , opioid , receptor , analgesic , protein kinase a , medicine , chemistry , endocrinology , biochemistry
The protein kinase C (PKC) family of serine–threonine kinases has been implicated in behavioral responses to opiates, but little is known about the individual PKC isozymes involved. Here, we show that mice lacking PKCɛ have increased sensitivity to the rewarding effects of morphine, revealed as the expression of place preference and intravenous self‐administration at very low doses of morphine that do not evoke place preference or self‐administration in wild‐type mice. The PKCɛ null mice also show prolonged maintenance of morphine place preference in response to repeated testing when compared with wild‐type mice. The supraspinal analgesic effects of morphine are enhanced in PKCɛ null mice, and the development of tolerance to the spinal analgesic effects of morphine is delayed. The density of μ‐opioid receptors and their coupling to G‐proteins are normal. These studies identify PKCɛ as a key regulator of opiate sensitivity in mice.