Rats were trained to discriminate the opioid receptor agonist ethylket
ocyclazocine (EKC) (0.3 mg/kg body weight, intraperitoneally) from sal
ine. Interferon-alpha (IFN-alpha), when substituted for EKC, elicited
a dose-related increase in EKC-like responses. This generalization of
EKC responses was blocked by the opioid antagonist naloxone (1 mg/kg).
Potentiation of responses to a low dose (0.1 mg/kg) of EKC by IFN-alp
ha (1 x 10(6) U/kg, or 0.22 nmol/kg) was also observed. Data thus indi
cate the involvement of opioid neurons on the action of IFN-alpha. d-A
mphetamine (0.8 mg/kg) was shown to potentiate both EKC (0.1 mg/kg) an
d IFN-alpha (1 x 10(6) U/kg). The present study confirms our previousl
y proposed opioid-mediated dopaminergic mechanism of IFN-alpha.