Involvement of mu-opioid receptor in the salsolinol-associated place preference in rats exposed to conditioned fear stress.
BACKGROUND
Salsolinol, a condensation product of dopamine with acetaldehyde (the initial oxidation product of ethanol), has long been discussed as an endogenous opioid system-activating factor contributing to the etiology of alcoholism. Moreover, psychological stress has been considered to play an important role in the development of alcoholism.


METHODS
Male Sprague Dawley rats were subjected to conditioned fear stress (at 24 hr after electric footshock exposure), and then salsolinol or saline was injected intraperitoneally. For conditioning, rats were immediately confined to the nonpreferred compartment after salsolinol injection and to the preferred compartment after saline injection on alternate days. This conditioning session was repeated twice daily (for 8 days). Test session was carried out 1 day after the last conditioning session.


RESULTS
Salsolinol [10 mg/kg, but not 1, 3, or 30 mg/kg, intraperitoneally (ip)] without conditioned fear stress induced a slight, but significant, place preference. In contrast, salsolinol (1, 3, and 10 mg/kg, ip) with conditioned fear stress induced a marked and significant place preference. The nonselective opioid receptor antagonist naloxone hydrochloride (which can pass into the brain), but not the nonselective peripheral opioid receptor antagonist naloxone methiodide (which cannot pass into the brain), significantly attenuated the salsolinol (3 mg/kg, ip)-induced place preference under conditioned fear stress. Moreover, the selective mu-opioid receptor antagonist beta-funaltrexamine significantly attenuated the salsolinol-induced place preference. Furthermore, 0.3 mg/kg salsolinol (which produced no significant place preference) combined with the mu-opioid receptor agonist morphine [0.1 mg/kg, subcutaneously (sc)], at the dose which alone produced no significant place preference, produced a marked and significant place preference. Both naloxone hydrochloride and beta-funaltrexamine significantly attenuated the salsolinol plus morphine-induced place preference.


CONCLUSIONS
Salsolinol may have some rewarding effect, and its rewarding effect may be potentiated by psychological stress. In addition, the rewarding effect of salsolinol especially under psychological stress may involve the endogenous central opioid system, i.e., mu-opioid receptor.