Experiments were carried out in rabbit cerebrocortical slices in order to find out whether the attenuation by presynaptic alpha 2-autoreceptors of effects mediated by presynaptic opioid kappa- and adenosine A1-receptors requires activation of the alpha 2-receptors. The slices were preincubated with 3H-noradrenaline and then superfused with medium containing desipramine 1 mumol/l. They were stimulated electrically either with single pulses or with trains of 32 pulses at 1 Hz. The overflow of tritium elicited by a single pulse amounted to 0.21% of the tritium content of the tissue. It was Ca2+-dependent and tetrodotoxin-sensitive and not changed by rauwolscine 1 mumol/l or yohimbine 0.3 mumol/l. Ethylketocyclazocine (EK; 0.1-10 nmol/l) and R-(-)-N6-phenylisopropyladenosine (PIA; 1-1,000 nmol/l) potently inhibited the overflow evoked by a single pulse, and their effects were not changed by yohimbine. - The overflow of tritium elicited by trains of 32 pulses at 1 Hz amounted to 0.92% of the tritium content of the tissue and was increased approximately fourfold by yohimbine 0.3 mumol/l. EK and PIA were less potent inhibitors than in the one pulse experiments. Yohimbine greatly enhanced the effects of EK and PIA. The enhancement was even more pronounced when the Ca2+ concentration in the medium was reduced in order to obtain a control tritium overflow similar to that evoked by 32 pulses in the absence of yohimbine. The results demonstrate that there is no alpha 2-adrenergic autoinhibition when noradrenaline release is elicited by a single pulse. Under these conditions, the non-activated presynaptic alpha 2-adrenoceptor does not interfere with presynaptic opioid kappa- and adenosine A1-receptor mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)