Modulation of noradrenaline release from cat cerebral arteries by presynaptic alpha 2-adrenoceptors. Effect of chronic treatment with desipramine and cocaine.

1. Field electrical stimulation elicited an increase of the tritium efflux over the basal level from cat cerebral arteries previously incubated with (+/-) [3H]noradrenaline ([3H]NA). 2. This efflux was: (a) reduced by clonidine, NA or B-HT 920; (b) unaffected by methoxamine, prazosin and yohimbine (10(-6) M); (c) reduced by yohimbine (5 x 10(-6) M), and (d) increased by phentolamine. 3. The effect of clonidine was blocked by yohimbine. 4. The daily treatment with the neuronal uptake blockers desipramine (10 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.) [during 12 days], antagonized the inhibitory action of clonidine totally or partially, respectively. 5. These results suggest: (1) the existence of presynaptic alpha 2-adrenoceptors in these arteries, which modulate the NA release, and (2) that chronic treatment with desipramine or cocaine induces a subsensitivity of these alpha 2-receptors, which facilitates the NA release.