Early exposure to haloperidol or olanzapine induces long-term alterations of dendritic form.
Exposure of the developing brain to a wide variety of drugs of abuse (e.g., stimulants, opioids, ethanol, etc.) can induce life-long changes in behavior and neural circuitry. However, the long-term effects of exposure to therapeutic, psychotropic drugs have only recently begun to be appreciated. Antipsychotic drugs are little studied in this regard. Here, we quantitatively analyzed dendritic architecture in adult mice treated with paradigmatic typical- (haloperidol) or atypical (olanzapine) antipsychotic drugs at developmental stages corresponding to fetal or fetal plus early childhood stages in humans. In layer 3 pyramidal cells of the medial and orbital prefrontal cortices and the parietal cortex and in spiny neurons of the core of the nucleus accumbens, both drugs induced significant changes (predominantly reductions) in the amount and complexity of dendritic arbor and the density of dendritic spines. The drug-induced plasticity of dendritic architecture suggests changes in patterns of neuronal connectivity in multiple brain regions that are likely to be functionally significant.
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 655 West Baltimore St., Baltimore, MD 21201, USA. dfrost@umaryland.edu
Douglas O
DO
Frost
Stephanie Cerceo
SC
Page
Cathy
C
Carroll
Bryan
B
Kolb
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D048430:Cell Shape / Q000187:drug effects*; D003712:Dendrites / Q000187:drug effects*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects; D000077152:Olanzapine; D010296:Parietal Lobe / Q000187:drug effects; D016622:Silver Staining; D013995:Time
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D006220:Haloperidol; D000077152:Olanzapine