Quantification of presynaptic alpha 2-adrenoceptors in rat brain after short-term DSP-4 lesioning.
The relative numbers of pre- and postsynaptic alpha 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 alpha 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 alpha 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 alpha 2-adrenoceptors comprise approximately 20% of the total alpha 2-adrenoceptor 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 alpha 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.
Heal
D J
DJ
Boots Pharmaceuticals Research Department, Nottingham, UK.
Butler
S A
SA
Prow
M R
MR
Buckett
W R
WR
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013563:Sympathectomy, Chemical; D015031:Zimeldine / Q000494:pharmacology
D018663:Adrenergic Agents; D001596:Benzylamines; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D015031:Zimeldine; C012102:DSP 4; D004298:Dopamine; D009638:Norepinephrine