title: Neonatal basolateral amygdala lesions affect monoamine and cannabinoid brain systems in adult rats.
abstract: There is evidence for neurodevelopment disturbances in schizophrenia. In rats, a neonatal basolateral amygdala lesion induces behavioural features in adults reminiscent of the symptomatology of schizophrenia. Dopamine plays a key role in the pathogenesis of schizophrenia, and cannabis use has been implicated in the risk for developing schizophrenia. The effects of an excitotoxic, bilateral basolateral amygdala lesion on postnatal days 7 or 21 were compared when the rats were adult. The behavioural response to a novelty challenge and the level of dopamine receptors and cannabinoid receptors in the brain using in-vitro autoradiography was determined. In brain tissue punches concentrations of monoamines and metabolites were determined by high-performance liquid chromatography. The neonatal lesion, but not the later lesion induced behavioural hyperactivity and biochemical effects. The neonatal lesion reduced the density of dopamine D2-like, but not D3-, and less markely D1-like receptors and increased dopamine turnover. These effects were observed in the mesolimbic, but not in the striatal regions. In contrast, density of cannabinoid receptors was increased in the striatal, but not the mesolimbic regions of these animals. Noradrenergic neurotransmission was reduced in both regions. The present findings contribute to the idea that the neonatal basolateral amygdala lesion induces features in adults reminiscent of the neurodevelopmental disturbances in schizophrenia, with a focus on the amygdala-prefrontal cortex-nucleus accumbens circuit.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Centre Utrecht, Utrecht University, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Bouwmeester
authors.forename: Mirjam A F M
authors.initials: MA
authors.lastname: Gerrits
authors.forename: John G
authors.initials: JG
authors.lastname: Roozemond
authors.forename: Jolanda
authors.initials: J
authors.lastname: Snapper
authors.forename: Eric
authors.initials: E
authors.lastname: Ronken
authors.forename: Chris G
authors.initials: CG
authors.lastname: Kruse
authors.forename: Herman G M
authors.initials: HG
authors.lastname: Westenberg
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Ree
mesh_terms: D000679:Amygdala / Q000473:pathology / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007051:Ibotenic Acid / Q000633:toxicity; D007091:Image Processing, Computer-Assisted; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D063385:Cannabinoid Receptor Modulators; D018690:Excitatory Amino Acid Agonists; D043884:Receptor, Cannabinoid, CB1; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D007051:Ibotenic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D009638:Norepinephrine