Table 3 Effect of nicotine on expression of genes involved in synaptic plasticity in the hippocampus, PFC, and amygdala of F344 rats. Significant expression alterations were determined by comparing the F344 nicotine-treated group with the F344 saline-treated group (Student’s t-test with Bonferroni correction). Significance set as p < 0.05 and fold ratio >20 %

Hippocampus

Ca⁺²/calmodulin-dependent kinase signaling

Camk4

Calmodulin-dependent protein kinase activity

3.3E-02 ± 1.1E-03

5.2E-02 ± 9.4E-04

1.57

0.007

Cacna1i

Voltage–gated calcium channel activity

2.0E-03 ± 3.6E-04

2.9E-03 ± 1.1E-04

1.46

0.03

PLC/IP3-mediated calcium signaling

Plcb4

Phospholipase C activity

2.4E-02 ± 2.2E-04

1.5E-02 ± 2.2E-03

0.66

0.02

Kinase signaling

Hras

GTPase activity

8.7E-06 ± 2.2E-06

4.1E-06 ± 1.7E-05

0.47

0.04

Prkacb

Protein kinase A activity

1.9E-02 ± 1.3E-03

1.5E-02 ± 1.6E-03

0.82

0.02

Adcy1

Adenylate cyclase activity

3.3E-01 ± 2.1E-02

2.6E-01 ± 2.1E-02

0.78

0.006

Mapk1

MAP kinase activity

4.3E-01 ± 2.1E-02

5.4E-01 ± 4.3E-03

1.25

0.01

Raf1

MAP kinase kinase activity

2.0E-02 ± 7.0E-04

3.0E-02 ± 2.1E-03

1.52

0.01

Map2k2

MAP kinase activity

2.3E-03 ± 1.7E-04

4.0E-03 ± 2.4E-04

1.73

0.001

Immediate early response gene

Ntrk2

Neurotrophin receptor activity

2.0E-03 ± 3.0E-04

1.1E-03 ± 5.1E-05

0.53

0.04

Egr1

Transcription factor activity

9.4E-02 ± 9.6E-03

5.3E-02 ± 5.7E-03

0.55

0.03

Jun-b

Transcription factor activity

1.5E-02 ± 2.2E-03

9.0E-03 ± 1.3E-03

0.57

0.02

Arc

Activity-regulated cytoskeleton-associated protein

1.2E-02 ± 2.0E-03

7.9E-03 ± 8.0E-04

0.63

0.03

Mmp9

Metallopeptidase activity

9.6E-05 ± 1.3E-05

1.8E-04 ± 3.5E-05

1.87

0.02

Prefrontal Cortex

Ionotropic glutamate receptor-mediated Ca⁺² influx

Grin2c

Ionotropic glutamate receptor

1.1E-02 ± 1.1E-03

8.5E-03 ± 5.2E-04

0.72

0.04

Grin2d

Ionotropic glutamate receptor

4.0E-03 ± 7.6E-05

3.0E-03 ± 1.0E-04

0.76

0.03

Ca⁺²/calmodulin-dependent kinase signaling

Camk2b

Calmodulin-dependent protein kinase activity

1.7E-01 ± 1.0E-02

2.9E-01 ± 2.3E-03

1.67

0.004

Cacna1g

Voltage–gated calcium channel activity

2.6E-02 ± 2.4E-03

4.0E-02 ± 2.5E-03

1.56

0.004

Camk4

Calmodulin-dependent protein kinase activity

3.3E-02 ± 2.1E-03

5.3E-02 ± 3.3E-03

1.60

0.002

Calm2

Calcium ion binding

4.4E-01 ± 6.0E-02

7.8E-01 ± 3.9E-02

1.73

0.001

PLC/IP3-mediated calcium signaling

Itpr2

Calcium ion transmembrane transporter activity

7.0E-03 ± 7.9E-04

4.6E-03 ± 3.3E-04

0.66

0.04

Plcb3

Phospholipase C activity

3.0E-03 ± 2.4E-04

2.0E-03 ± 2.6E-04

0.68

0.03

Itpr1

Calcium ion transmembrane transporter activity

7.0E-03 ± 7.9E-04

5.1E-01 ± 6.9E-04

0.73

0.01

Kinase signaling

Raf1

MAP kinase kinase activity

2.0E-02 ± 7.0E-04

1.4E-02 ± 1.8E-03

0.72

0.03

Mapk3

MAP kinase activity

6.6E-02 ± 3.9E-03

4.9E-02 ± 1.1E-03

0.74

0.006

Prkacb

Protein kinase A activity

1.9E-02 ± 1.3E-03

2.3E-02 ± 4.7E-03

1.15

0.01

Akt1

Akt kinase activity

4.2E-02 ± 2.6E-03

5.0E-02 ± 3.1E-03

1.26

0.02

Adcy8

Adenylate cyclase activity

3.9E-03 ± 4.2E-04

5.1E-03 ± 2.4E-04

1.31

0.02

Immediate early response gene

Synpo

Actin binding

3.4E-02 ± 2.6E-03

4.4E-02 ± 2.8E-03

1.27

0.04

Ngf

Growth factor activity

1.5E-03 ± 1.6E-04

1.9E-03 ± 7.2E-05

1.29

0.03

Inflammation-mediated neurodegenerative signaling

Il-6

Cytokine activity

1.5E-4 ± 1.5E-05

7.0E-05 ± 7.8E-06

0.45

0.001

Tnf

Cytokine activity

4.2E-04 ± 1.1E-04

3.0E-04 ± 2.8E-05

0.70

0.04

Amygdala

Ca⁺²/calmodulin-dependent kinase signaling

Calm1

Calcium ion binding

1.2 ± 9.0E-02

9.2E-01 ± 7.8E-02

0.75

0.04

Camk2g

Calmodulin-dependent protein kinase activity

3.2E-2 ± 2.4E-03

2.5E-02 ± 1.6E-03

0.80

0.04

PLC/IP3-mediated calcium signaling

Itpr2

Calcium ion transmembrane transporter activity

6.8E-03 ± 4.2E-04

5.5E-03 ± 1.0E-04

0.80

0.02

Itpr3

Calcium ion transmembrane transporter activity

3.6E-03 ± 3.4E-04

3.0E-03 ± 7.7E-05

0.82

0.03

Kinase signaling

Mapk1

MAP kinase activity

2.7E-01 ± 2.2E-02

1.5E-01 ± 2.0E-01

0.55

0.007

Raf1

MAP kinase kinase activity

2.5E-02 ± 1.5E-03

1.8E-02 ± 2.0E-03

0.72

0.02

Immediate early response gene

Fos-b

Transcription factor activity

1.0E-02 ± 3.2E-03

3.8E-03 ± 9.7E-04

0.38

0.03

Junb

Transcription factor activity

1.5E-02 ± 2.2E-0

8.0E-03 ± 1.4E-03

0.51

0.02

Egr1

Transcription factor binding activity

9.4E-02 ± 9.7E-03

5.8E-02 ± 3.8E-03

0.61

0.01

Ntrk2

Neurotrophin receptor activity

4.3E-03 ± 5.7E-04

2.6E-03 ± 1.9E-04

0.61

0.02

Bdnf

Growth factor activity

9.2E-05 ± 5.3E-06

5.8E-05 ± 1.6E-05

0.63

0.03

Fos

Transcription factor activity

3.0E-03 ± 5.0E-04

1.9E-03 ± 2.0E-04

0.63

0.04