Quantification of presynaptic α2-adrenoceptors in rat brain after short-term DSP-4 lesioning

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The relative numbers of pre- and postsynaptic α 2-adrenoceptors were determined in various rat brain regions after short-term DSP-4 ( N-(2-chloroethyl)- N-ethyl-2-bromobenzylamine) lesioning. For these studies, rats pretreated with zimeldine (10 mg/kg i.p.) were injected with DSP-4 (100 mg/kg i.p.) and were killed either 3 or 15 days later. At the 3 day time-point, DSP-4 treatment produced marked reductions in the noradrenaline content of the cortex (93%), hippocampus (89%), hypothalamus (83%) and cerebellum (92%) with no change in the levels of dopamine or 5-HT. This treatment also decreased the number of α 2-adrenoceptors labelled with [ 3H]idazoxan in the cortex (20%), hippocampus (18%), cerebellum (24%) and hypothalamus (39%). Fifteen days after DSP-4 lesioning, the marked reductions of noradrenaline were sustained in the cortex, hippocampus and cerebellum, but there was a considerable reversal of the effect of DSP-4 in the hypothalamus. At this time-point, the decrease in α 2-adrenoceptors was attenuated in cortex (4%) and cerebellum (0%) and their number was increased in hippocampus (8%) and hypothalamus (7%). Together, the data argue that presynaptic α 2-adrenoceptors comprise approximately 20% of the total α 2-adrenoceptors population in the cortex, hippocampus and cerebellum, but about 40% of it in the hypothalamus. Furthermore, they also demonstrate that although the number of presynaptic α 2-adrenoceptors in rat brain can be determined by the reduction of radioligand-receptor binding shortly after DSP-4 lesioning, this effect is rapidly masked by receptor proliferation in response to noradrenergic denervation.