Differential Induction of Fos-Like-Immunoreactivity in the Extended Amygdala after Haloperidol and Clozapine

Abstract

The extended amygdala is composed of the central and medial amygdaloid nucleus which through the sublenticular extended amygdala (SLEA) and the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) merge into the bed nucleus of stria terminals (BST). Based on anatomical connections with limbic areas, the extended amygdala has been proposed to play an important role in cognitive and affective processes. This study examines the effect of the atypical antipsychotic clozapine and the classical antipsychotic haloperidol on Fos-like-immunoreactivity (FLI) induction in areas belonging to the extended amygdala.Acute administration of clozapine (10-20 mg/kg) The amygdaloid complex is an ensemble of nuclei that play a central role in emotional processes, particularly in the assignment of affective significance to specific stimuli (Aggleton 1993;Aggleton and Mishkin 1985;Gallagher and Chiba 1996;Le Doux 1995). Information elaborated in the basolateral amygdaloid nuclei enter into the central amygdaloid nucleus, which conveys the stimuli together to elicit appropriate behavioral responses (Pitkänen et al. 1997).Neuronal cell groups composing the central and medial amygdaloid nucleus form a continuum of cells that extend through the sublenticular extended amygdala (SLEA) and the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) to merge with the bed nucleus of stria terminalis (BST) and form the socalled extended amygdala (Alheid and Heimer 1988;Alheid et al. 1995;Heimer et al. 1997b).The central division of the extended amygdala, which is formed by the central amygdaloid nucleus, BST lateral division, IPAC, and SLEA central division, establishes reciprocal neuronal connections with the caudal aspect of the nucleus accumbens shell (Acb shell) and is also connected with the prefrontal cortex (de Olmos et al. 1985;Heimer et al. 1997a;Heimer et al. 1997b;Zahm and Brog 1992 Based on anatomical connections, the extended amygdala seems to be an important site involved in neuropsychiatric disorders (Heimer et al. 1997b); however, specific data showing the effect of drugs used in the therapy of these disorders in the extended amygdala are scarce. Induction of the early gene c-fos by antipsychotics in the central amygdaloid nucleus (Sebens et al. 1995) and antagonism of the excitatory effects induced by a local infusion of amphetamine in the amygdaloid complex by clozapine (Wang and Rebec 1996) have been reported. Moreover, it was recently shown (Beck 1994;Duncan et al. 1996;Morelli et al. 1999) that antidepressant drugs inhibiting either noradrenaline or serotonin re-uptake, induced the expression of the early gene c-fos in areas belonging to the rat extended amygdala, suggesting a role of the extended amygdala in disorders characterized by affective disturbance.Induction of the early gene c-fos is secondary to neuronal activation and is correlated to an increased function of specific areas in the CNS (Sagar et al. 1988). Moreover, detection of the c-fos-encoded protein Fos, throug...

Effects of Aripiprazole and Haloperidol on Fos-like Immunoreactivity in the Prefrontal Cortex and Amygdala

“…We observed a significant increase in FLI in the Ce and BL after all doses (1.0, 10 or 30 mg/kg) of aripiprazole, but a low dose of 0.1 mg/kg of haloperidol produced a significant increase in FLI only in the Ce and BL. These findings regarding haloperidol treatment are consistent with the findings of other studies,23,24) implying that haloperidol has a limited effect in this area. On the other hand, clozapine (10-20 mg/kg)23) and olanzapine (10 mg/kg)24) both produce a significant increase in FLI in the Amyg.…”

The evolving theory of basal forebrain functional—anatomical ‘macrosystems’

“…de Olmos, 1972;de Olmo and Ingram, 1972;Haber et al, 1985;Koob, 1999;McDonald, 2003;Morelli et al, 1999;Newman and Winans, 1980;Pinna and Morelli, 1999), including in the primate (e.g. Haber and Gdowski, 2003;Martin et al, 1991;Meredith et al, 1996;Voorn et al, 1996), the macrosystem described by Alheid and Heimer (1988) as centered on the lateral septum and diagonal band, in contrast, has been less well represented in subsequent literature (but see Swanson, 2000).…”

Cells in midline thalamus, central amygdala, and nucleus accumbens responding specifically to antipsychotic drugs

“…Evidence from several laboratories suggests that cells of the midline thalamic nuclei respond to all neuroleptics (McCulloch et al 1982;Deutch et al 1995;Cohen and Wan 1996;Cohen et al 1998). There are also observations that the central amygdala may activate in response to neuroleptics (Pizzolato et al 1984;Pinna and Morelli 1999;Ma et al 2000).…”