LOCOMOTOR INHIBITION, YAWNING AND VACUOUS CHEWING INDUCED BY A NOVEL DOPAMINE D-2 POSTSYNAPTIC RECEPTOR AGONIST

The N-n-propyl analog of dihydrexidine ((+/-)-trans-10,11-dihydroxy-5, 6,6 a,7,8,12 b-hexahydrobenzo[a]phenanthridine) is a dopamine receptor agonist with high affinity for dopamine D-2 and D-2 receptors (K-0.5= 26 and 5 nM, respectively). Members of the hexahydrobenzo[a]phenanthri dine structural class are atypical because they display high intrinsic activity at post-synaptic dopamine D, receptors, but low intrinsic ac tivity at dopamine D, autoreceptors. The present study examined the ef fects of(+/-)-N-n-propyl-dihydrexidine on unconditioned behaviors in r ats. The most striking results observed were large, dose-dependent dec reases in locomotor activity (e.g,, locomotor inhibition), and increas es in vacuous chewing; yawning was also increased at the highest dose of(+/-)-N-n-propyl-dihydrexidine The locomotor inhibition and yawning induced by (+/-)-N-n-propyl-dihydrexidine were blocked by pre-treatmen t with (-)-remoxipride yl-2-pyrrolidinyl)-methyl)-2,6-dimethoxybenzami de) a dopamine D-2 receptor antagonist, but not by the dopamine D-1 re ceptor antagonist(+)-SCH23390 o-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-te trahydro-1 H-3-benzazepine). Vacuous chewing was decreased by both (-) -remoxipride and (+)-SCH23390. These data support the hypothesis that a subpopulation of post-synaptic dopamine D-2 receptors has a critical role in decreases in locomotor activity and induction of vacuous chew ing and yawning. (C) 1997 Elsevier Science B.V.