RT Journal Article
SR Electronic
T1 Influence of chronic lithium treatment upon the motivational effects of opioids: alteration in the effects of mu- but not kappa-opioid receptor ligands.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1101
OP 1106
VO 256
IS 3
A1 T S Shippenberg
A1 A Herz
YR 1991
UL http://jpet.aspetjournals.org/content/256/3/1101.abstract
AB The influence of chronic lithium (Li) treatment upon the secondary reinforcing effects of opioid agonists and antagonists was examined by use of an unbiased place preference conditioning procedure. Administration of the mu-agonist morphine to control rats resulted in marked preferences for the drug-associated place and a similar effect was observed in response to the psychostimulant d-amphetamine. In contrast, the selective kappa-opioid agonist U-69593 [(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-1(pyrrolidinyl-1-oxaspirol(4,5) dec-8-yl benzeneacetamide)] and the opioid antagonist naloxone produced dose-related place aversions. Chronic administration of a Li-containing diet, which produced serum levels of 0.56 mmol/l, abolished the place preferences induced by morphine but not d-amphetamine. This treatment abolished the aversive effects of naloxone but did not modify those produced by U-69593. These data and those from a previous place conditioning study indicate that Li can function as an antagonist of mu-opioid receptor ligands in vivo and that this action underlies its motivational effects. Furthermore, the inability of chronic Li treatment to modify either the content or basal release of beta-endorphin in various brain regions suggests that this antagonism is mediated directly at the level of the opioid receptor and/or its transducer systems.