NeuropharmacologyDynorphinergic gaba neurons are a target of both typical and atypical antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus and thalamic central medial nucleus
Section snippets
Animal subjects
Sprague–Dawley rats (Charles River, Wilmington, MA, USA; body weight 320–350 g) were maintained in groups of three to four per cage with food and water ad libitum in a room with a 12-h light/dark cycle. Rats were frequently handled in the days before the study to reduce the effects of stress associated with drug treatment. Our required minimum number of animals were treated in accordance with the provisions of the “Guide for the Care and Use of Laboratory Animals” of the United States
The expression of clozapine- and haloperidol-induced Fos protein is not colocalized with astrocytes in AcbSh, CeA and CM
The location of the double labeled cells in the present study is shown schematically in Fig. 1. The immunoreactive specificity was verified with the control experiment as described in the previous section on experimental procedure. No clozapine-induced Fos-positive cells stained for GFAP, a specific marker for astrocytes, as shown in Fig. 2. Similar results were seen in haloperidol treated rats (Table 1). Thus, clozapine and haloperidol target no astrocytes as their sites of action.
The expression of clozapine- and haloperidol-induced Fos proteins is colocalized with dynorphin-containing GABAergic neurons in AcbSh, CeA and CM
Fos staining
Discussion
In previous studies, we and others have consistently demonstrated that both haloperidol and clozapine are able to induce Fos expression in AcbSh, CeA and CM Deutch et al., 1992, Robertson and Fibiger, 1992, Robertson et al., 1994, Wan et al., 1995, Cohen and Wan, 1996, Sebens et al., 1995, Cohen et al., 1998, Suzuki et al., 1998, Pinna and Morelli, 1999, Cohen et al., 2003. The studies reported here were designed to identify which specific cell types in these regions respond to antipsychotic
Conclusion
In summary, we have examined which cell types in the AcbSh, CeA and CM respond to typical antipsychotic drug haloperidol and atypical antipsychotic agent clozapine. Using double immunofluorescence labeling with antibodies directed against markers specific to candidate cell types, we have demonstrated that both haloperidol and clozapine activate dynorphinergic GABA neurons, but do no appear to activate other cell types examined, including astrocytes, acetylcholinergic neurons and
Acknowledgements
This work was supported by NIH grants (MH31154, NS37483), the Stanley Foundation and the Engelhard Foundation.
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