Investigating the Role of P-CREB and c-Fos protein Expression in Nicotine-Induced Anxiogenesis in Rats

Nicotine is one of the most common addictive substances that has many effects on the central nervous system, including dose-dependent anxiety that is mediated by various proteins. Since the mechanisms and proteins involved in nicotine anxiety are unclear, the purpose of the present study was to investigate the role of p-CREB (cAMP Response Element-Binding Protein) and c-Fos proteins in the basolateral amygdala (BLA) on nicotine-induced anxiety behaviours.

In this experimental study, 24 male Wistar rats were divided into three groups of 7 (saline, nicotine 0.3 and 0.7 mg/kg, intraperitoneally) in behavioral experiment and four groups of 3 (control: no injection and test, Saline, nicotine 0.3 and 0.7 mg/kg) in immunohistochemical experiments. Anxiety-like behaviours were evaluated with % OAT (Open Arm Time), %OAE (Open Arm Entry), and locomotor activity in the elevated plus maze. The expression of p-CREB and c-Fos proteins in BLA region was also assessed by immunohistochemistry.

Intraperitoneal administration of nicotine at a dose of 0.7mg/kg decreased %OAT (5.4±0.42) and %OAE (29.4±0.61) compared to saline group (15.2±0.82) and (42.1±0.45), indicating an anxiety-like effect (respectively, p<0.001, p<0.01). In addition, there was a significant difference in the expression of p-CREB (H(3)= 6.99, p<0.05) and c-Fos (H(3)=13.11, p<0.01) protein in the BLA between treatment groups. P-CREB protein expression was higher in the BLA area of control group than in the other groups. C-Fos protein expression was significantly lower in the BLA region of the animals of control, nicotine 0.3 mg/kg and 0.7 mg/kg groups compared to saline group (p<0.01).

The results of this study indicated that systemic administration of nicotine induced anxiety-like behaviors at high doses. Also, the expression of P-CREB and c-Fos protein was unchanged and decreased in the treatment groups, respectively.