Korean J Physiol Pharmacol.  2013 Oct;17(5):405-409. 10.4196/kjpp.2013.17.5.405.

Sex Differences in Hippocampal Neuronal Sensitization by Nicotine in M. gerbils

• Hur YN
• Lee J
• Sohn SC
• Won CG
• Lee HH
• Kim DH
• Choi SH
• Shin KH
• Chun BG

• KMID: 1500234
• DOI: http://doi.org/10.4196/kjpp.2013.17.5.405

Abstract

We studied the sex different nicotine effect on evoked population spike amplitudes (ePSA) and connexin (Cx) expression in the hippocampus CA1 area of gerbils. Acute doses of nicotine bitartrate (0.5 mg/kg: NT-0.5) slightly reduced ePSA in males but markedly augmented that in females. Acute NT (5.0 mg/kg) markedly increased the ePSA in all gerbils. Unlike acute NT-0.5, repeated NT-0.5 injection (twice a day for 7 days) significantly increased the ePSA in males and slightly affected the NT-0.5 effect in females. The Cx36 and Cx43 expression levels as well as Cx expressing neuronal populations were significantly increased by repeated NT-0.5 in in both male and female gerbils, and particularly, Cx43 expression was somewhat prominent in females. These results demonstrated a sex difference with respect to the nicotine effect on hippocampal bisynaptic excitability, irrelevant to connexin expression.

Keyword

Connexin; Evoked population spike; Hippocampus; Nicotine; Sex difference

MeSH Terms

Animals
Connexins
Connexin 43
Female
Gerbillinae*
Hippocampus
Male
Neurons*
Nicotine*
Sex Characteristics*
Connexins
Connexin 43
Nicotine

Figure

• 

  Fig. 1 Illustrations of the recording of evoked population spike amplitude (ePSA). (A) Position of stimulating and recording electrodes in the hippocampus CA1 area. (B) Patterns of evoked population spikes recorded in different levels of the pyramidal neuron. (C) Dose-dependent nicotine effect on ePSA in male gerbils. Saline, saline, 1 ml/kg i.p. injection; NT-0.5, nicotine bitartrate, 0.5 mg/kg, i.p. injection; NT-5.0, nicotine bitartrate, 5.0 mg/kg, i.p. injection.

• 

  Fig. 2 Acute and repeated nicotine effects on evoked population spike amplitude. (A) Sex-related difference in the response of ePSA to NT-0.5 and NT-5.0, respectively. Symbols: ○, saline, 1 ml/kg i.p. injection; •, NT-0.5: nicotine bitartrate, 0.5 mg/kg, i.p. injection; ▴, NT-5.0: nicotine bitartrate, 5.0 mg/kg, i.p. injection. (B) Responses of ePSA to a challenging NT-0.5 in male and female gerbils pretreated with repeated injections of NT-0.5 s.c., twice per day for 7 days or 28 days. ○, acute NT-0.5 injection; •, pretreatment with NT-0.5 for 7 days; ▴, pretreatment with NT-0.5 for 28 days. Each bar represents the mean±SE (n=5 or 6). * and ** indicate p<0.05 and p<0.01, respectively, compared to control groups: (A) saline group and (B) NT-0.5 group.

• 

  Fig. 3 Double immunohistochemistry photographs. (A) The oriens (Or), pyramidal (Py) and radiatum (Rad) layers in the hippocampus CA1 area (×200); (B) anti-NeuN immunoreactive neurons, (C) anti-Cx36 immunoreactive dots; (D) merged image of B and C (×600). Scale bars: (A) 50 µm and (D) 7 µm.

• 

  Fig. 4 Increases of (A) anti-Cx36 and (B) anti-Cx43 IR dots by a challenging NT-0.5 in gerbils pretreated with repeated NT-0.5 injections twice a day for 7 days. The following data were obtained from 5 animals by blind counting in a predefined region (300×400 µm2) of the pyramidal layer in serial 16 images per animal. * and ** indicate p<0.05 and p<0.01, respectively, in comparison to the saline treated group. †Means p<0.05, with respect to comparisons between male and female groups. anti-Cx36, -Cx43 dots, total count of anti-Cx36, -Cx43 IR dots; anti-Cx36, -Cx43 dots/Neuron, count of anti-Cx36, -Cx43 IR dots per an anti-NeuN IR neuron; anti-Cx36, -Cx43 IR+Neurons, count of anti-NeuN IR neurons with anti-Cx36, -Cx43 IR dots. SS & SN, Saline & NT-0.5 challenge after repeated saline pretreatment for 7 days; NS & NN, Saline & NT-0.5 challenge after repeated NT-0.5 pretreatment for 7 days.

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