Cataleptic and anticataleptic effects of muscimol and gabaculine injected into globus pallidus and substantia nigra, and interactions with haloperidol or benzodiazepines

Abstract

Intranigral injection of muscimol induced hyperactivity in rats and antagonized haloperidol-induced catalepsy. Intranigral injection of gabaculine, an inhibitor of GABA transaminase, induced similar effects 5h after injection, when the nigral GABA content was increased 7-fold. On the other hand, injections of muscimol (30 ng) into the globus pallidus potentiated the cataleptic effect of haloperidol, and muscimol alone in high doses (100 and 200 ng) induced catalepsy. Gabaculine also induced catalepsy of medium intensity and potentiated the effect of haloperidol 24h after injection, when GABA was increased in the globus pallidus as well as in the substantia nigra. Injections of muscimol into either the globus pallidus or substantia nigra increased striatal HVA and enhanced haloperidol-induced elevation of HVA. Three benzodiazepines, nitrazepam, diazepam and chlordiazepoxide administered orally, potentiated the effect of muscimol (30 ng) injected into the globus pallidus and induced catalepsy. A similar effect was not obtained with phenobarbital. It is suggested that stimulation of GABA receptor or increase of GABA content in the sustantia nigra antagonize haloperidol-induced catalepsy by activation of nigral dopaminergic system, and that enhancement of pallidal GABA function induces catalepsy by non-dopaminergic mechanisms. Potentiation of haloperidol-induced catalepsy by benzodiazepines may be due to enhancement of GABA-ergic transmission within the globus pallidus.

Motor effects of GABA A antagonism in globus pallidus: studies of locomotion and tremulous jaw movements in rats

“…In addition, it is important to emphasize that in experiment 1, in which no other drug treatments were given, bicuculline increased locomotor counts, as well as focused locomotion and circling. The present results are in agreement with early studies of the effects of GABAergic manipulations in GP on locomotion and catalepsy (Pycock et al 1976;Matsui and Kamioka 1978; -Kruger 1983;Ossowska et al 1984), and also are consistent a more recent study showing that bicuculline reversed reserpine-induced motor suppression (Brotchie et al 1993). The present results, as well as the previous findings, are generally consistent with current functional models of the basal ganglia (Alexander and Crutcher 1990;Carlsson 1993;Filion and Tremblay 1991).…”

“…Drug treatments acting on either DA or ACh systems were used to induce jaw movement activity (i.e., 14 days of 0.5-mg/ kg haloperidol, or acute injection of 4.0-mg/kg pilocarpine), and the same treatments were used in parallel studies of locomotor activity. The D2 antagonist haloperidol suppresses locomotion and induces catalepsy (Matsui and Kamioka 1978;Worms and Lloyd 1980;Balsara et al 1980;Svensson et al 1993), and also induces jaw movements Rupniak et al 1983Rupniak et al , 1985Salamone et al 1998). Although the induction of jaw movements with haloperidol can occur after a single acute injection, the effect is typically more robust after a few days of repeated injections Salamone et al, 1998;Trevitt et al, 1998).…”

“…Locomotion and catalepsy are thought to be related to akinesia, and these motor tests have been used previously to study the functions of GP GABA (Pycock et al 1976;Williams and Herberg 1987;Matsui and Kamioka 1978;ScheelKruger 1983;Scheel-Kruger et al 1981a, 1981bOssowska et al 1984;Amalric and Koob 1989;Brotchie et al 1993). In addition, drug-induced tremulous jaw movements in rats have been used as a model of parkinsonian tremor Rodriquez Diaz et al 2001).…”

Endomorphin-1: Induction of Motor Behavior and Lack of Receptor Desensitization

“…Similar to the effects of endomorphin-1, previous studies have shown that the local administration of the GABA receptor antagonist bicuculline in the globus pallidus stimulates dyskinesia (Crossman et al, 1988;Matsumura et al, 1995). In contrast, both local administration of the GABA agonist muscimol in the globus pallidus and chronic peripheral treatment with the opioid antagonist naloxone induced catalepsy in rats (Matsui and Kamioka, 1978;Egan et al, 1995). Thus, endomorphin and GABA induce opposite behavioral effects in the globus pallidus.…”

“…Because local administration of a GABA agonist (Matsui and Kamioka, 1978) or dopamine antagonists (Hauber and Lutz, 1999) in the globus pallidus has been shown to induce catalepsy in rats, we tested for this behavior after the administration of endomorphin-1. Bilateral infusion of endomorphin-1 (18 pmol per side) into the globus pallidus did not induce catalepsy when tested 15, 30, 60, 90, and 120 min postinfusion (n ϭ 4; data not shown).…”