Long-term increase in GAD67 mRNA expression in the central amygdala of rats sensitized by drugs and stress.
Repeated administration of addictive drugs and prolonged exposure to stressful stimuli induce sensitization to their behavioural stimulant properties. In this study, male Sprague-Dawley rats were repeatedly exposed to morphine [twice a day for 3 days at increasing doses, 10, 20, 40 mg/kg subcutaneously (s.c)], amphetamine (1 mg/kg s.c., once a day for 10 days), nicotine (0.4 mg/kg s.c., once a day for 5 days) and stress (food restriction for 7 days). After an interval of 3-30 days, depending on the pretreatment, rats were challenged with vehicle, with the same drug received as pretreatment (5 mg/kg of morphine, 0.5 mg/kg of amphetamine or 0.4 mg/kg of nicotine, respectively) or, in the case of food-restricted rats, with 0.5 mg/kg of amphetamine. Thereafter, changes in the expression of glutamic acid decarboxylase (GAD)67 mRNA were estimated by in situ hybridization in the central nucleus of the amygdala (CeA), basolateral amygdala (BLA), dorsolateral striatum (dLStr), nucleus accumbens shell (AcS) and core (AcC). All sensitizing pretreatments increased GAD67 mRNA in the CeA. Drug challenge did not further affect GAD67 mRNA in the CeA of saline, drug and stress pre-exposed rats. As to the other areas, no differences were observed in drug pre-exposed compared with saline pre-exposed and fed ad libitum rats, except for amphetamine. Amphetamine pre-exposure decreased GAD67 mRNA levels in the dLStr and the AcC and AcS, and this effect was reversed by amphetamine challenge. The results show that different drugs and stress models of behavioural sensitization have in common an increase of GA67 in the CeA but not in the BLA, and suggest the changes of GAD67 in the CeA are a substrate of the sensitized response to drug challenge.
Carta
Anna R
AR
Department of Toxicology, University of Cagliari, Cagliari, Italy. acarta@unica.it
Moreno
Carmen Casal
CC
Cadoni
Cristina
C
Tronci
Elisabetta
E
Di Chiara
Gaetano
G
D000679:Amygdala / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D005508:Food Deprivation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D013287:Illicit Drugs / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000201:enzymology* / Q000235:genetics / Q000523:psychology; D013995:Time
D013287:Illicit Drugs; D012333:RNA, Messenger; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1