Persistent activation of select forebrain regions in aggressive, adolescent cocaine-treated hamsters.
Hamsters repeatedly exposed to cocaine throughout adolescence display highly escalated offensive aggression compared to saline-treated littermates. The current study investigated whether adolescent cocaine exposure activated neurons in areas of hamster forebrain implicated in aggressive behavior by examining the expression of FOS, i.e., the protein product of the immediate early gene c-fos shown to be a reliably sensitive marker of neuronal activation. Adolescent cocaine-treated hamsters and saline-treated littermates were scored for offensive aggression and then sacrificed 1 day later and examined for the number of FOS immunoreactive (FOS-ir) cells in regions of the hamster forebrain important for aggression control. When compared with non-aggressive, saline-treated controls, aggressive cocaine-treated hamsters showed persistent increases in the number of FOS-ir cells in several aggression regions, including the anterior hypothalamus, nucleus circularis, lateral hypothalamus (i.e., the hypothalamic attack area), lateral septum, and medial and corticomedial amygdaloid nuclei. Conversely, aggressive cocaine-treated hamsters showed a significant decrease in FOS-ir cells in the medial supraoptic nucleus, bed nucleus of the stria terminalis, and central amygdala when compared with controls. However, no differences in FOS-ir cells were found in other areas implicated in aggression such as the paraventricular hypothalamic nucleus, or in a number of non-aggression areas. These results suggest that adolescent cocaine exposure may constitutively activate neurons in select forebrain areas critical for the regulation of aggression in hamsters. A model for how persistent activation of neurons in one of these brain regions (i.e., the hypothalamus) may facilitate the development of the aggressive phenotype in adolescent cocaine-exposed animals is presented.
Knyshevski
Irina
I
Behavioral Neuroscience Program, Department of Psychology, 125 Nightingale Hall, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
Connor
Daniel F
DF
Harrison
Robert J
RJ
Ricci
Lesley A
LA
Melloni
Richard H
RH
D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects* / Q000502:physiology; D000367:Age Factors; D000374:Aggression / Q000502:physiology*; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D006224:Cricetinae; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004334:Drug Administration Schedule; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008647:Mesocricetus; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011897:Random Allocation; D018709:Statistics, Nonparametric
D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D003042:Cocaine