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 (ED(50) 0.088 mg/kg). This response was maximal when measured 10 min after clonidine inject ion and was of about 30-min duration. The noradrenaline releasing agen t, methamphetamine (0.75 mg/kg, IP), also increased pupil diameter. Cl onidine (0.03 mg/kg, IP)-induced mydriasis was inhibited in a dose-rel ated 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 th e alpha(1)- or beta-adrenergic antagonists, prazosin (1 and 3 mg/kg, I P) or pindolol (1 and 3 mg/kg, IP). Methamphetamine (0.75 mg/kg, IP)-i nduced mydriasis was similarly inhibited by idazoxan (1 mg/kg, IP) and yohimbine (1 mg/kg, IP). These data argued strongly that central alph a(2)-adrenoceptors are involved in the mediation of mydriasis. The syn aptic location of these receptors was determined using DSP-4 (50 mg/kg x 2, IP) to lesion noradrenergic neurones: this produced a 64% deplet ion 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 c lonidine mydriasis remained unaltered. Therefore, these results show t hat the mydriasis responses induced by either clonidine or methampheta mine are mediated by central postsynaptic alpha(2)-adrenoceptors.