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Endogenous enkephalins, not endorphins, modulate basal hedonic state in mice
P D Skoubis1, H A Lam, J Shoblock
1Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, University of California at Los Angeles, Los Angeles, CA 90024, USA.
The European Journal of Neuroscience
|April 9, 2005
Summary
Enkephalins, not endorphins, appear to regulate the brain's hedonic tone, as shown by naloxone aversion tests in knockout mice. This suggests enkephalins play a key role in mood regulation.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Pharmacology
Background:
- Endogenous opioid peptides influence hedonic state, but their specific roles are unclear.
- Naloxone administration elicits aversive responses, indicating an existing opioid tone.
- The precise opioid peptides mediating this tone require identification.
Purpose of the Study:
- To investigate the roles of beta-endorphin and enkephalins in mediating the aversive effects of naloxone.
- To determine which opioid peptide class underlies the endogenous opioid tone regulating hedonic state.
Main Methods:
- Utilized a naloxone-conditioned place aversion paradigm in mice.
- Compared wild-type, beta-endorphin-deficient, and pro-enkephalin knockout mice.
- Administered naloxone or saline over three days and assessed chamber preference.
Main Results:
- Pro-enkephalin knockout mice did not exhibit naloxone-induced aversion, unlike wild-type and beta-endorphin-deficient mice.
- Pro-enkephalin knockout mice retained normal associative learning for other stimuli (U50,488, LiCl) and morphine reward.
- These findings implicate enkephalins, but not endorphins, in the basal opioid tone.
Conclusions:
- Enkephalins, rather than endorphins, likely mediate the endogenous opioid component of basal affective state.
- The release of endogenous enkephalins or endorphins is not critical for learning reward associations with exogenous opioids.