Adfærdsmæssig interaktion mellem en ny glutamat-antagonist, FG 9065, og dopamin-agonister hos aber

Abstract

Lublin H, Gerlach J. Behavioral interaction between a new glutamate antagonist, FG 9065, and dopamine agonists in monkeys.

Glutamatergic mechanisms have been found to be involved in regulation of the dopaminergic system. The effects of glutamate are mediated by two groups of receptors: the N-rnethyl-D-aspartate (NMDA) receptors and the non-NMDA receptors, one of the latter being of the quisqualate type. FG 9065 (a quisqualate antagonist) was evaluated in eight Cebus monkeys, which previously had received haloperidol for 2 years. Five monkeys had mild oral tardive dyskinesia, consisting of tongue protrusions and/or chewing movements. FG 9065 was evaluated alone and in combination with methylphendiate (dopamine-releasing and uptake-inhibiting drug), SKF 38393 (partial dopamine D-1 agonist), and quinpirole (LY 171555, selective dopamine D-2 agonist). FG 9065 induced/aggravated oral tardive dyskinesia. Otherwise no behavioral effects were found. Methylphenidate increased locomotor activity, stereotypy, and reactivity. SKF 38393 increased oral tardive dyskinesia and grooming, whereas locomotor activity was reduced, probably due to sedation. Quinpirole increased locomotor activity, stereotypy, and reactivity, whereas oral hyperkinesia and grooming were decreased. Pretreatment with FG 9065 inhibited the methylphenidate-induced stereotypy and reactivity, aggravated SKF 38393-induced grooming behavior and reduced the quinpirole-induced locomotor activity, repetitive movements, and reactivity. The results confirm the existence of an interaction between the glutamatergic and dopaminergic systems. FG 9065 antagonized the effect of methylphenidate and the D-2 agonist. If these results can be confirmed in following studies, they might indicate neuroleptic and therefore therapeutic properties of this group of drugs.

Key Words:

• Dopaminergic system
• Glutamatergic system
• Quisqualate antagonist
• Tardive dyskinesia