Effects of Bilateral Lesions in the Striatum or Nucleus Accumbens on the Cataleptogenic Activity of Neuroleptics in Rats

Abstract

Abstract-To investigate the role of the striatum and nucleus accumbens in neuroleptic induced catalepsy, bilateral electrocoagulations were made or microinjections of 6-hydroxydopamine (6-OHDA) were given to rats in these brain regions, and the cata leptogenic activity of neuroleptics was measured. Electrocoagulation in these regions caused a highly specific destruction of brain tissue, and 6-OHDA decreased the levels of dopamine in the injected region with little effect on these levels in other regions. The cataleptogenic activity of haloperidol was enhanced by the electrocoagulation in the striatum at 2 days after the operation, but was weakened from 7 days on. The elec trocoagulation weakened the catalepsy induced by chlorpromazine, thioridazine, and ID-4708 (a new butyrophenone derivative), but enhanced that by clozapine at 2 weeks after the operation.Microinjection of 6-OHDA into the striatum enhanced the catalepsy induced by the five neuroleptics used. The lesions in the nucleus accum bens had fewer effects on catalepsy than did those in the striatum. It was concluded that the striatum more than the nucleus accumbens is involved in producing cata lepsy with neuroleptics, and that the enhancement of catalepsy by electrocoagula tion in the striatum is characteristic of clozapine.Pharmacological, biochemical and electrophysiological investigations showed that neuroleptics block dopamine (DA) receptors in the brain (1-3). Almost all neuroleptics produce catalepsy in rats. Reserpine and tetrabenazine reduce the monoamine contents and produce catalepsy (4, 5). These facts suggest that the catalepsy is the result of blockade of DA receptors or the reduction of the activity of DA neurons (6). DA containing nerve terminals are localized in the striatum and nucleus accumbens (7). Therefore, the catalepsy may be induced by the effect of drugs on these brain regions. The present study was under taken to investigate the contribution of DA neurons in the striatum (extrapyramidal system) and nucleus accumbens (mesolimbic system) to the catalepsy induced by neuroleptics.There are data as to the effects of electrocoagulation in the caudate-putamen on the catalep togenic activity of several neuroleptics (8, 9). We investigated the effects of electrocoagu lation in the striatum or nucleus accumbens on the cataleptogenic activity of haloperidol, ID-4708 (a new butyrophenone derivative), chlorpromazine, thioridazine and clozapine.Effects of microinjection of 6-hydroxydopamine (6-OHDA) into the striatum or nucleus accumbens on the cataleptogenic activity of these five neuroleptics were also investigated.

Multiple neurochemical action of clozapine: A quantitative autoradiographic study of DA 2, opiate and benzodiazepine receptors in the rat brain after long-term treatment

“…According to electrophysiological and behavioral data (Burki etal., 1975;Kelly and Iversen, 1976;Pijnenburg et al, 1976;Honma and Fukushima, 1978), our results confirm that the preferential target of the DA-ergic action of clozapine is the mesolimbocortical system. After chronic clozapine treatment, we found a decrease of the DA 2 receptor only in the n. accumbens and in the ventral n. caudate-putamen.…”

The Mechanism of Action of Novel Antipsychotic Drugs

“…Some behavioral studies of DA agonist effects mediated by the striatum (stereotypy, catalepsy) or nucleus accumbens (locomotor activity) indicate a limbic selectivity for CLOZ (Burki et al 1975; Iversen and Koob 1977; Honma and Fukushima 1978; Ljunberg and Ungerstedt 1978). However, CLOZ can block the effect of electrical stimulation of the substantia nigra on turning behavior in rats, an effect mediated in the striatum (Roffman et al 1978).…”

Brain tyrosine depletion attenuates haloperidol-induced striatal dopamine release in vivo and augments haloperidol-induced catalepsy in the rat

“…For instance, HALinduced catalepsy is attenuated by intrastriatal administration of d-amphetamine (Costall et al 1972b). In contrast, DA depleting lesions of the striatum augment HAL catalepsy (Honma and Fukushima 1978;Dunstan et al 1981;Jaskiw et al, unpublished data). Similarly, the DA synthesis inhibitor a-methylparatyrosine blocks the HAL-induced increase in striatal DA release and/or potentiates HAL-induced catalepsy (Costall and Naylor 1975;Shore and Dorris 1975).…”