Mediation of mydriasis in conscious rats by central postsynaptic alpha 2-adrenoceptors.
The alpha 2-adrenoceptor agonist, clonidine (0.001-1 mg/kg, IP), dose-dependently induced mydriasis in conscious rats (ED50 0.088 mg/kg). This response was maximal when measured 10 min after clonidine injection and was of about 30-min duration. The noradrenaline releasing agent, methamphetamine (0.75 mg/kg, IP), also increased pupil diameter. Clonidine (0.03 mg/kg, IP)-induced mydriasis was inhibited in a dose-related fashion by the alpha 2-adrenoceptor antagonists, idazoxan (0.03-3 mg/kg, IP) and yohimbine (0.03-3 mg/kg, IP), but was unaltered by the alpha 1- or beta-adrenergic antagonists, prazosin (1 and 3 mg/kg, IP) or pindolol (1 and 3 mg/kg, IP). Methamphetamine (0.75 mg/kg, IP)-induced mydriasis was similarly inhibited by idazoxan (1 mg/kg, IP) and yohimbine (1 mg/kg, IP). These data argued strongly that central alpha 2-adrenoceptors are involved in the mediation of mydriasis. The synaptic location of these receptors was determined using DSP-4 (50 mg/kg x 2, IP) to lesion noradrenergic neurones: this produced a 64% depletion of noradrenaline in the midbrain (containing the Edinger-Westphal nucleus responsible for mydriasis) and reduced the mydriatic effect of methamphetamine (0.75 mg/kg, IP) to a similar extent (72%), whereas clonidine mydriasis remained unaltered. Therefore, these results show that the mydriasis responses induced by either clonidine or methamphetamine are mediated by central postsynaptic alpha 2-adrenoceptors.
Heal
D J
DJ
Boots Pharmaceuticals Research Department, Nottingham, UK.
Prow
M R
MR
Butler
S A
SA
Buckett
W R
WR
D018663:Adrenergic Agents / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009184:Mydriatics / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D011680:Pupil / Q000187:drug effects; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D018663:Adrenergic Agents; D058669:Adrenergic alpha-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D001596:Benzylamines; D015306:Biogenic Monoamines; D009184:Mydriatics; D018341:Receptors, Adrenergic, alpha-2; D017981:Receptors, Neurotransmitter; D008694:Methamphetamine; D003000:Clonidine; C012102:DSP 4