STIMULATORY EFFECTS OF CLONIDINE, CIRAZOLINE AND RILMENIDINE ON LOCUS-CERULEUS NORADRENERGIC NEURONS - POSSIBLE INVOLVEMENT OF IMIDAZOLINE-PREFERRING RECEPTORS

Clonidine and related drugs not only interact with alpha2-adrenoceptor s but also recognise non-adrenoceptor sites in the brain. The involvem ent of these imidazoline-preferring receptors in the regulation of the activity of locus coeruleus noradrenergic neurones (NA-LC) was invest igated after inactivation of alpha2-adrenoceptors with N-ethoxycarbony l-2-ethoxy-1,2-dihydroquinoline (EEDQ). In EEDQ-pretreated rats (6 mg/ kg, i.p., 6 h), the characteristic inhibitory effect of low doses of c lonidine on these neurones was abolished and a paradoxical, dose-depen dent increase in firing rate was observed at higher doses (640-5120 mu g/kg, iv.) (ED50 = 702 mug/kg, E(max) = 83%, n = 14). Guanfacine (0.3- 20 mg/kg) did not modify neuronal activity but antagonised the stimula tory effect of clonidine. Cirazoline (80-640 mug/kg) and rilmenidine ( 0.3-10 mg/kg) also stimulated neuronal activity (ED50 = 192 mug/kg, E( max) = 102%, n = 5; ED50 = 1563 mug/kg, E(max) = 70%, n = 1-5, respect ively) by an alpha2-adrenoceptor-independent mechanism. The results su ggest that these drugs can modulate the activity of locus coeruleus no radrenergic neurones through the activation of I1-imidazoline-preferri ng receptors.