Cocaine- and alcohol-mediated expression of inducible transcription factors is blocked by pentobarbital anesthesia.
Identifying the neurocircuitry involved in behavioral responses to drugs of abuse is an important step towards understanding the mechanisms of drug addiction. The present study sought to distinguish brain regions involved in pharmacological effects of cocaine and ethanol from secondary effects by administering these drugs in the presence or absence of pentobarbital anesthesia. Changes in neuronal activity were assessed by immunohistochemical analysis of expression of an inducible transcription factor (ITF), c-Fos, in the brain of rats habituated to repeated pentobarbital anesthesia or saline administration. Cocaine administration (15 mg/kg, i.v.) in non-anesthetized animals produced a strong induction of c-Fos in the striatum and large number of other brain areas. Ethanol administration (2 g/kg, i.p.) induced c-Fos in a smaller number of characteristic brain areas, including the central nucleus of amygdala and paraventricular nucleus of hypothalamus. However, neither of these drugs was able to induce c-Fos in pentobarbital-anesthetized rats (50 mg/kg, i.v.). The suppressive effects of pentobarbital were not specific to c-Fos, such that pentobarbital also suppressed expression of ITFs FosB and Egr1 in the striatum of cocaine-treated rats. On the other hand, pentobarbital by itself strongly induced c-Fos expression in the lateral habenula of saline-, cocaine-, and ethanol-injected rats. It is not clear whether the suppressive effects of anesthesia on ITF expression in other areas are mediated by activation of lateral habenula, or are independent of this event. Our data suggest that in the absence of conscious awareness of drug-associated cues, cocaine and alcohol activate only a fraction of the neural elements engaged in the unanesthetized state.
Ryabinin
A E
AE
Department of Behavioral Neuroscience, L470, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA. ryabinin@ohsu.edu
Wang
Y M
YM
Bachtell
R K
RK
Kinney
A E
AE
Grubb
M C
MC
Mark
G P
GP
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D004347:Drug Interactions / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism
D000777:Anesthetics; D001426:Bacterial Proteins; D002352:Carrier Proteins; C400751:Cuzd1 protein, rat; C483820:Fosb protein, rat; D008565:Membrane Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D000431:Ethanol; D010424:Pentobarbital; D003042:Cocaine