Extended Amygdala Research Articles

Effects of the dopamine D-1 antagonist SCH 23390 microinjected into the accumbens, amygdala or striatum on cocaine self-administration in the rat

This study tested the hypothesis that blockade of D-1 dopamine receptors in the nucleus accumbens shell, central nucleus of the amygdala or dorsal striatum by intracerebral microinjection of the dopamine antagonist SCH 23390 produces an attenuation of the effects of self-administered cocaine. Microinjection of SCH 23390 (0–4.0 μg total dose) into any of the three brain regions dose-dependently increased the rate of cocaine self-administration, consistent with a partial attenuation of the effects of cocaine under these conditions (0.25 mg cocaine i.v.; fixed-ratio 5 timeout 20 s). The regional rank order potency of SCH 23390 was accumbens > amygdala > striatum, striatal injections being equipotent with subcutaneous administration. Moreover, SCH 23390 produced rapid effects on cocaine self-administration only when injected into the accumbens or amygdala. The time course of this regional selectivity was consistent with the rate of diffusion of SCH 23390 from the site of injection as measured by quantitative autoradiography, demonstrating that the regional selectivity of intracerebral injections of SCH 23390 is time-dependent. These results support a role for D-1 dopamine receptors in the nucleus accumbens and amygdala in the effects of self-administered cocaine, and suggest that D-1 receptors in certain portions of the ‘extended amygdala’ may be an important substrate for the reinforcing actions of cocaine.

Evidence for a GABAergic interface between cortical afferents and brainstem projection neurons in the rat central extended amygdala

The synaptic circuitry of the intrinsic GABAergic system of the central extended amygdala (CEA) in relation to efferent neurons and cortical afferents was examined in the present study. Neurons in the CEA projecting to the dorsal vagal complex and the parabrachial complex were identified by the retrograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Postembedding GABA-immunocytochemistry revealed that GABA-immunoreactive (GABA-IR) terminals formed largely symmetrical synaptic contacts with the perikarya and proximal dendritic processes of almost all WGA-HRP-labeled neurons in the CEA. To determine the relationship between cortical afferents and CEA GABAergic neurons, WGA-HRP was used to anterogradely label afferents from the insular cortex in combination with postembedding immunogold detection of GABA. Cortical afferents formed asymmetrical synaptic contacts predominantly on small dendrites and dendritic spines. Many of the dendrites postsynaptic to cortical terminals in the central nucleus were immunoreactive for GABA although only relatively few spines were GABA-IR. Combining pre-embedding GAD-immunocytochemistry with cortical lesions resulted in approximately 40% of degenerating terminals of insular cortical origin in the central nucleus in contact with small, GAD-IR dendrites and spines. The present results demonstrate that the neurons providing the major CEA outputs to the brainstem receive an extensive GABAergic innervation, strongly supporting our proposal that CEA efferent neurons are under strong tonic inhibition by intrinsic GABAergic neurons. Further, our finding that the major cortical input to the central nucleus preferentially innervates intrinsic GABAergic neurons suggests that these neurons in the CEA may serve as an interface between the principal inputs and outputs of this forebrain region.

Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat

The distribution of dopaminergic fibers in the principal components of the central extended amygdala (central amygdaloid nucleus (Ce), substantia innominata, and bed nucleus of the stria terminals (BNST)), was studied using immunocytochemistry against tyrosine hydroxylase, dopamine β-hydroxylase and dopamine. Dopamine fibers were found most densely distributed in the dorsolateral subdivision of the BNST and the lateral part of the Ce. Smaller numbers of dopaminergic fibers were found in the rest of the central extended amygdala. In contrast, dopamine β-hydroxylase fibers were virtually absent from the dorsolateral bed nucleus of the stria terminalis and lateral part of the central amygdaloid nucleus, but were distributed in a moderate density in the medial part of Ce, dorsal substantia innominata and posterolateral BNST. Our results show that dopamine fibers are most concentrated over those regions of the central extended amygdala with large numbers of GABAergic neurons whose projections remain within the central extended amygdala, while noradrenergic fibers are most heavily concentrated over those regions containing a large proportion of brainstem projection neurons. That dopamine fibers are concentrated over regions with GABAergic medium spiny neurons suggests that those regions might be organized as a striatal parallel.

Intrinsic GABAergic neurons in the rat central extended amygdala

The present study examined the distribution, morphology, and connections of gamma-aminobutyric acid-immunoreactive (GABA-IR) neurons in the three principal components of the central extended amygdala: the central amygdaloid nucleus, the bed nucleus of the stria terminalis (BNST) and the sublenticular substantia innominata. In the central nucleus, large numbers of GABA-IR neurons were identified in the lateral, lateral capsular, and ventral subdivisions, though in the medial subdivision, GABA-IR neurons were only present at very caudal levels. Combined immunocytochemistry-Golgi impregnation revealed that GABA-IR neurons in the lateral central nucleus were medium-sized spiny neurons that were morphologically similar to GABAergic neurons in the striatum. Injections of horseradish peroxidase into the bed nucleus of the stria terminalis labeled a major proportion of the GABA-IR neurons in the central nucleus. In the bed nucleus, the majority of GABA-IR neurons were located in the anterolateral subdivision, ventral part of the posterolateral subdivision and the parastrial subdivision. GABA-IR neurons in the anterolateral bed nucleus were of the typical medium-sized spiny type. Injections of horseradish peroxidase into the central nucleus labeled a few GABA-IR neurons in the posterior part of the anterolateral bed nucleus. GABA-IR neurons were identified in the sublenticular substantia innominata and medial shell of the nucleus accumbens and contributed to the continuum of GABA-IR extending from the central nucleus to the bed nucleus. Injections of horseradish peroxidase (HRP) into the central nucleus, but not the BNST, labeled a few GABA-IR neurons in the substantia innominata. The data point to GABA-IR neurons being a characteristic feature of the central extended amygdala and that GABA-IR neurons participate in the long intrinsic connections linking the major components of this structure. Since lesions of the stria terminalis and basolateral amygdaloid nucleus failed to deplete GABA-IR terminals in the central nucleus, the role of GABA in local and short intrinsic connections in the central extended amygdala is discussed. Further, physiological findings implicating the intrinsic GABAergic system of the central extended amygdala in the tonic inhibition of brainstem efferents are reviewed.

The substantia innominata complex and the peripeduncular nucleus in orofacial dyskinesia: A pharmacological and anatomical study in cats

It has been shown that orofacial dyskinesia, i.e. a syndrome of abnormal involuntary movements of the facial muscles, can be elicited from the sub-commissural part of the globus pallidus and the adjoining dorsal parts of the extended amygdala in cats. Until now it is unknown whether the peripeduncular nucleus, which receives input from these structures according to anterograde tracing studies, plays a role in the funneling of orofacial dyskinesia to lower output stations. In the present study the connection of the subcommissural part of the globus pallidus and dorsal parts of the extended amygdala with the peripeduncular nucleus was investigated anatomically, using cholera toxin subunit B as a retrograde tracer, and functionally, using intracerebral injections of GABAergic compounds. The anatomical data show that the sub-commissural part of the globus pallidus and dorsal parts of the extended amygdala were marked by cholera toxin sub-unit B-immunoreactive cells following injections of this retrograde tracer into the peripeduncular nucleus. Thus, it could be confirmed that the peripeduncular nucleus receives input from the sub-commissural part of the globus pallidus and dorsal parts of the extended amygdala. Still, the orofacial dyskinesia elicited by local injections of the GABA antagonist picrotoxin (500 ng/0.5 ml) into the sub-commissural part of the globus pallidus and dorsal extended amygdala was only in part attenuated by local injections of the GABA agonist muscimol (100 ng/l ml) into the peripeduncular nucleus. Only the number of tongue protrusions was significantly attenuated, but not that of the ear and cheek movements. Furthermore, tongue protrusions, but no additional oral movements, were elicited by picrotoxin injections (375–500 ng) into the peripeduncular nucleus. However, these effects were dose dependent and could only be elicited from the dorsal parts of the peripeduncular nucleus. Injections into the ventral parts of the extended amygdala were ineffective in every respect in the present investigation. The data show that the peripeduncular nucleus does not funnel the orofacial dyskinesia from the sub-commissural part of the globus pallidus and dorsal parts of the extended amygdala to lower brain structures despite the fact that it is innervated by the former regions. The finding that the peripeduncular nucleus itself is only involved in the modulation of the display of tongue protrusions may explain why manipulations with the peripeduncular nucleus only affected this aspect of the orofacial dyskinesia elicited from the sub-commissural part of the globus pallidus and dorsal parts of the extended amygdala.

New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: The striatopallidal, amygdaloid, and corticopetal components of substantia innominata

The basal forebrain is critically involved in functions representing the highest levels of integration. Only recently has a relatively clear anatomical picture of this important area begun to emerge. The territory that has generally been referred to as the “substantia innominata” appears to be composed of portions of three recognizable forebrain structures: the ventral striatopallidal system, the extended amygdala and the magnocellular corticopetal system. (1) Rostrally, the striatopallidal system reaches ventrally to the base of the brain. (1) Caudal to the ventral extension of the striatopallidal system elements of the centromedial amygdala and bed nucleus of the stria terminalis are merged so that these two areas together with this subpallidal corridor form a large forebrain unit that might be described as an “extended amygdala”. (1) Large cholinergic and non-cholinergic corticopetal neurons form a more or less continuous aggregate that is interwoven with the striatopallidal and extended amygdala systems in basal forebrain. Consideration of morphological and conneetional characteristics of basal forebrain suggests that the corticopetal cell groups, together with magnocellular elements of the striatum. serve similar functional roles for the strialopallidal system, the extended amygdala, and the septal diagonal band complex. Specifically, the output of medium spiny neurons in striatum, extended amygdala, and lateral septum are directed toward somewhat larger sparsely or moderately spiny neurons with radiating dendrites which in turn project to diencephalon and brainstem or provide either local feedback (e.g. in striatum) or distal feedback to cortex. The functional implications of this parallel processing of descending forebrain afferents are discussed.

Medial forebrain bundle-lateral hypothalamic area and reinforcing brain stimulation.

Medial forebrain bundle, lateral hypothalamic area and reinforcing brain stimulation, discussing self-stimulation