The mGluRs group II agonist (2S,3S,4S)-alpha-carboxycyclopropyl-glycine induces catalepsy in the rat, which is pronouncedly antagonised by dizocilpine and D,L-amphetamine.
Glutamate in the basal ganglia has important roles in the regulation of motor processes and this is the first study on the role of inhibitory, group II, metabotropic glutamate receptors (mGluRs) for motor behaviour. The group II agonist (2S,3S,4S)-alpha-carboxycyclopropyl-glycine (L-CCG I) dose dependently induced catalepsy, infused intracerebroventricular (i.c.v.) in rats. The catalepsy was antagonised by dizocilpine and D,L-amphetamine, i.e. by N-methyl-D-aspartate receptor blockade and dopamine receptor activation, respectively. Psychotomimetic side effects limit the clinical use of previously suggested postsynaptic approaches to reduce pathological glutamatergic overactivation, as occuring in epilepsy, ischemia or trauma, but group II agonists provide a new presynaptic approach. Since the catalepsy-induction predicts a lack of psychotomimetic side effects, this study indicates that presynaptic approaches on mGluRs may be more suitable in these situations.
Kronthaler
U O
UO
Department of Neuropharmacology, University of Tübingen, Germany. ulrich.kronthaler@uni-tuebingen.de
Schmidt
W J
WJ
D000600:Amino Acids, Dicarboxylic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000600:Amino Acids, Dicarboxylic; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; C035261:(alpha-carboxycyclopropyl)glycine; D016291:Dizocilpine Maleate; D000661:Amphetamine