Modulation of rat brain alpha-adrenoreceptor populations four weeks after stimulation of the nucleus locus coeruleus.
We previously showed that electrical stimulation of the nucleus locus coeruleus was followed 4 weeks later by a greatly improved performance in the acquisition of a food-reinforced operant task. To ascertain whether adrenergic receptors were involved in this long-term behavioral modification, we studied the characteristics of the alpha 1, alpha 2, and beta-adrenoreceptors of the cerebral cortex 4 weeks after stimulation of the locus coeruleus. This stimulation induced a slight (14%) but significant increase in the number of alpha 1-receptor [(3H) WB 4101 binding sites] as well a rise in the number of alpha 2-receptor [(3H) clonidine binding sites]. The latter rise mainly affected high-affinity alpha 2-receptor sites (36%) and the number of low-affinity sites remained unchanged. No significant alteration in the number of beta-receptors [(3H)-dihydroalprenolol binding sites] was observed. To confirm this biochemical result, the effect of very small doses of clonidine (1, 2.5, 5 and 10 micrograms/kg) was tested on locomotor activity in the open-field. In rats stimulated 4 weeks before injection, clonidine induced a biphasic effect, comprising firstly sedation which occurred 30 min after injection, and secondly, long-term hyperactivity which began 24 h injection. For the 5 micrograms/kg dose, this rebound of activity was detectable 8 days after injection. In implanted, control rats, only the sedative effect was observed. These findings are interpreted in relation to the current theories about alpha-adrenoreceptors.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004082:Dihydroalprenolol; D004146:Dioxanes; D004558:Electric Stimulation; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism / Q000502:physiology*
D004146:Dioxanes; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D004082:Dihydroalprenolol; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine