Premium
Behavioral synergism between D 1 and D 2 dopamine receptors in mice does not depend on gap junctions
Author(s) -
Nolan Eileen B.,
Harrison Laura M.,
Lahoste Gerald J.,
Ruskin David N.
Publication year - 2007
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20371
Subject(s) - eticlopride , receptor , chemistry , dopamine receptor d2 , sch 23390 , dopamine receptor , raclopride , agonist , endocrinology , medicine , pharmacology , quinpirole , biology , biochemistry
Activation of the D 1 and D 2 classes of dopamine receptor in the striatum synergistically promotes motor stereotypy. The mechanism of D 1 /D 2 receptor interaction remains unclear. To investigate the involvement of electrical synaptic transmission in this phenomenon, genetic inactivation of the neuronal gap junction (GJ) protein connexin 36 and pharmacological blockade of GJs were utilized. Stereotyped motor behavior was quantified after selective activation of D 1 receptors, D 2 receptors, or both receptors. These patterns of activation were produced by injection of the agonist apomorphine (3.0 mg/kg) 30 min after either the D 2 antagonist eticlopride (0.3 mg/kg), the D 1 antagonist SCH 23390 (0.1 mg/kg) or vehicle, respectively. Mixed background C57/BL6–129SvEv mice homozygous or heterozygous for the connexin 36 “knockout” allele displayed potent synergistic interaction between D 1 and D 2 receptor activation, and did not differ significantly from wild‐type mice on any measure. All genotypes demonstrated long‐lasting stereotypic sniffing, chewing, and/or licking after simultaneous activation of D 1 and D 2 receptors, effects that were absent following selective D 1 or D 2 activation. Swiss‐Webster mice treated with the GJ blockers carbenoxolone (35 mg/kg), octanol (350 mg/kg) or mefloquine (50 mg/kg) also demonstrated the normal synergistic interaction between D 1 and D 2 receptors, although these drugs did block the grooming stimulated by selective D 1 receptor activation, independently of D 2 receptors. While D 1 receptor‐stimulated grooming depends on GJs composed of connexins or possibly pannexins, the synergistic interaction of D 1 and D 2 receptors in control of stereotypy does not involve GJs. Synapse 61:279–287, 2007. © 2007 Wiley‐Liss, Inc.