Endogenous opioid pathways (EOPs) appear to play a role in the tonic regulation of pulsatile LH secretion. The mechanism by which EOPs influence LH release is not known. However, the observation that acute chemical disruption of the noradrenergic (NE) system by alpha-receptor-blocking agents or NE synthesis inhibitors blocks the LH increase occurring in response to naloxone (NAL) suggests that the ability of EOPs to influence LH secretion may depend upon a functional NE system. We hypothesized that if EOPs required an interacting NE system to influence LH secretion, then rats that have ascending NE tract lesions would not respond to NAL with an increase in LH. To test this hypothesis, we challenged NE-lesioned and sham-lesioned rats with NAL. Young adult male rats received either a NE lesion or a sham lesion and 6 weeks later were implanted with jugular catheters. On the following day, four baseline blood samples (400 microliters at 10-min intervals) were taken from NE-lesioned and sham-lesioned rats. All rats were then challenged with 2 mg/kg NAL, iv, and four subsequent blood samples were taken. NAL significantly increased LH levels (P less than 0.01) in both the NE-lesioned (n = 7) and sham-lesioned (n = 8) rats. Mean LH responses above baseline for these groups were 0.52 +/- 0.12 ng RP-2/ml and 0.38 +/- 0.07 ng/ml, respectively. Failure of the NE lesions to block the LH response to NAL was not due to the presence of active residual NE fibers, because pretreatment with the alpha-receptor blocker phenoxybenzamine (20 mg/kg, iv) failed to block the NAL response in the NE-lesioned animals (n = 8), whereas it did so in the sham-lesioned animals (n = 7). The mean LH response from baseline after phenoxybenzamine pretreatment was -0.01 +/- 0.01 ng/ml for the sham-lesioned group and 0.53 +/- 0.24 ng/ml for the NE-lesioned group. These results indicate that EOPs do not require noradrenergic mediation to influence LH secretion in the adult male rat.