title: Repeated cocaine exposure during adolescence alters glutamic acid decarboxylase-65 (GAD65) immunoreactivity in hamster brain: correlation with offensive aggression.
abstract: Male Syrian hamsters (Mesocricetus auratus) treated with low-dose (0.5 mg/kg/day) cocaine throughout adolescence (P27-P56) display highly escalated offensive aggression. The current study examined whether adolescent cocaine exposure influenced the immunohistochemical localization of glutamic acid decarboxylase-65 (GAD65), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), a fast-acting neurotransmitter implicated in the modulation of aggression in various species and models of aggression. Hamsters were administered low doses of cocaine throughout adolescence, scored for offensive aggression using the resident-intruder paradigm, and then examined for changes in GAD65 immunoreactivity in areas of the brain implicated in aggression control. When compared with saline-treated control animals, aggressive cocaine-treated hamsters showed significant differences in the area covered by GAD65 puncta in several notable aggression regions, including the anterior hypothalamus, the medial and central amygdaloid nuclei, and the lateral septum. However, no differences in GAD65 puncta were found in other aggression areas, such as the bed nucleus of the stria terminalis, the ventrolateral hypothalamus, and the corticomedial amygdala. Together, these results suggest that altered GABA synthesis and function in specific aggression areas may be involved in adolescent cocaine-facilitated offensive aggression.
authors.affiliation: Program in Behavioral Neuroscience, Department of Psychology-125 NI, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Ricci
authors.forename: Jill M
authors.initials: JM
authors.lastname: Grimes
authors.forename: Irina
authors.initials: I
authors.lastname: Knyshevski
authors.forename: Richard H
authors.initials: RH
authors.lastname: Melloni
mesh_terms: D000367:Age Factors; D000374:Aggression / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D003042:Cocaine / Q000008:administration & dosage*; D006224:Cricetinae; D004334:Drug Administration Schedule; D005968:Glutamate Decarboxylase / Q000032:analysis / Q000378:metabolism*; D007120:Immunochemistry; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus
chemical_list: D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D003042:Cocaine