Central alpha-2 adrenoceptors are responsible for a clonidine-induced cue in a rat drug discrimination paradigm.
Clonidine produces an interoceptive discriminative stimulus or "cue" in rat drug discrimination studies. This cue may be mediated by its alpha-2 adrenoceptor agonist properties and/or its affinity for the non-adrenoceptor imidazoline preferring receptor. Six rats were trained to respond differentially after receiving clonidine (0.02 mg kg-1, IP) or a saline vehicle. The alpha-2 adrenoceptor agonists clonidine, UK14, 304 and rilmenidine, which bind to the imidazoline preferring receptor, and guanabenz which does not, dose-dependently substituted for (i.e. > 80% total responding was clonidine associated) the clonidine-induced cue in doses up to 0.02, 0.16, 1.25 and 0.32 mg kg-1, respectively. Furthermore, the cue was blocked when clonidine was given in combination with 30-min pretreatments of the highly selective alpha-2 adrenoceptor antagonists RX811059 (2.5 mg kg-1) and fluparoxan (3 mg kg-1). Since the clonidine-induced cue was substituted for by guanabenz, which does not act at the imidazoline-preferring receptor, and antagonised by RX811059 and fluparoxan it appears to be mediated by alpha-2 adrenoceptors. Moreover, abolition of the clonidine-induced cue did not occur with the peripherally acting alpha-2 adrenoceptor antagonist L659, 066 suggesting it involves central as opposed to peripheral sites.
Jordan
S
S
Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.
Jackson
H C
HC
Nutt
D J
DJ
Handley
S L
SL
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004192:Discrimination, Psychological / Q000187:drug effects*; D008297:Male; D010080:Oxazoles / Q000494:pharmacology; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D012055:Reinforcement Schedule; D012201:Reward; D000077769:Rilmenidine
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D010080:Oxazoles; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine; D000077769:Rilmenidine