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Background: Nicotine is a major toxic and hazardous component of cigarette smoke, and it has been widely used in nicotine replacement therapy (NRT). This study was aimed to investigate the effects of chronic low-dose nicotine on sperm characteristics and reproductive organ integrity in adolescent male Sprague--Dawley rats. Methods: Twelve rats were equally divided into two groups. Group I received normal saline, and group II received 0.6 mg/kg body weight nicotine intraperitoneally for 28 consecutive days. At the end of the experimental period, sperm was collected for sperm characteristic evaluation, and the testes and prostate were isolated for biochemical and morphological analysis. The effects of nicotine on the body and reproductive organ weights of the animals were evaluated. Results: Chronic nicotine treatment significantly (P < 0.05) altered the sperm count, motility, viability, and morphology, and remarkably increased the malondialdehyde (P < 0.001) and advanced oxidation protein product (P < 0.05) levels in the testes and prostate of nicotinetreated group compared to control group. Moreover, nicotine caused a significant decrease (P < 0.05) in the superoxide dismutase activity of the testes. No significant differences were observed in the reduced glutathione level in both of the testes and prostate of nicotine group compared with control group. Nicotine also induced histopathological alteration in the testes. Conclusion: A low-dose nicotine exposure at 0.6 mg/kg caused detrimental effects on sperm characteristics and induced oxidative stress in the testes and prostate. [ABSTRACT FROM AUTHOR]

Abstract: Nicotine withdrawal may differ between men and women but clinical reports are inconsistent. Two experiments were conducted to examine behavioral effects of nicotine withdrawal in male and female adult rats in dimly-lit and brightly-lit environments. Ninety-six Sprague–Dawley male and female rats received 7 days continuous subcutaneous infusion via ALZET osmotic minipumps filled with saline or 3.16 mg/kg/day nicotine hydrogen tartrate expressed as base. Behavioral observations were made before, during, and after drug administration. During observations, occurrences of empty-mouth-chewing, whole-body-shakes, abnormal grooming, abnormal posture/movement, diarrhea, ptosis, eyeblinks, and any other abnormal behaviors were counted. Cessation of nicotine administration upon pump removal caused a significant increase in withdrawal behaviors in males and females in both environments. In the dimly-lit environment, females showed more withdrawal behavior than males; there was no sex difference in the brightly-lit environment. Males that had received nicotine displayed more withdrawal behavior in the brightly-lit environment than in the dimly-lit environment, while females that had received nicotine displayed similar amounts of withdrawal behavior in both environments. Behavioral symptoms of withdrawal may be more affected by the environment in male rats than in female rats. These experiments are the first to compare nicotine withdrawal in adult male and female rats. [Copyright &y& Elsevier]

Abstract: Adolescence is the life stage when tobacco addiction typically begins. Adolescent neurobehavioral development may be altered by nicotine self-administration in a way that persistently potentiates addiction. Previously, we showed that female adolescent rats self-administer more nicotine than do adults and that the increased nicotine intake then persists through the transition to adulthood [E.D. Levin, A. Rezvani, D. Montoya, J. Rose, H. Swartzwelder, Adolescent-onset nicotine self-administration modeled in female rats, Psychopharmacology 169 (2003) 141–149.]. In the current study, male Sprague–Dawley rats were given access to nicotine via the standard operant IV self-administration procedure (nicotine bitartrate dose of 0.03 mg/kg/infusion). One group of male rats started during adolescence the other group started in young adulthood. After the end of the four-week period of self-administration brain regions of the rats were assessed for α4β2 nicotinic receptor binding. We found that male rats, like females, show higher nicotine self-administration when starting during adolescence as compared to starting in adulthood (p <0.001). Indeed, the effect in adolescent males was even greater than that in females, with more than triple the rate of nicotine self-administration vs. the adult-onset group during the first 2 weeks. The adolescent onset nicotine-self-administering rats also had significantly greater high affinity nicotinic receptor binding in the midbrain and the striatum, whereas hippocampal binding did not differ between the age groups. Striatal values significantly correlated with nicotine self-administration during the first 2 weeks in the adult-onset group but not the adolescent-onset rats, suggesting that the differences in self-administration may depend in part on underlying disparities in synaptic responses to nicotine. After the initial 2 weeks, nicotine self-administration in male rats declined toward adult-like levels, as the adolescent rats approached adulthood. This study showed that adolescent male rats self-administer significantly more nicotine than do male adult rats, but that adolescent-onset nicotine self-administration in male rats declines over weeks of continued use to approach adult-onset levels. In a previous study, we found that female rats also show greater nicotine self-administration with adolescent onset vs. adult onset, but that the females continued higher rates of self-administration into adulthood. Our results thus reinforce the concept that the adolescent brain is unusually receptive to the effects of nicotine in a manner that reinforces the potential for addiction. [Copyright &y& Elsevier]

Abstract: The present study aimed to evaluate whether housing condition could interact with nicotine administration in influencing the acquisition of a two-way active avoidance task. Male NMRI mice were either group- or individually housed for 30 days and, after this period, evaluated both in the actimeter and, 24h later, in the elevated plus-maze. On the basis of the percentage of time spent in the open arms of the plus-maze, both group- and individually housed mice were sub-classified into three groups with high, moderate or low anxiety baseline levels. Effects of nicotine on the acquisition of the two-way active avoidance task was assessed in each of these groups of mice using an automated shuttle-box. Mice were treated with nicotine (0.35mg/kg) or vehicle before each daily training session in the shuttle-box (30 trials) over 5 days. The results showed that motor activity counts were significantly higher in individually housed mice than in group-housed counterparts. The factor “anxiety” in the active avoidance test did not reach statistical significance but the factor “housing” did. The number of avoidances was higher in individually housed than in group-housed mice. Separate analyses performed for individually and group-housed animals indicated that group-housed nicotine-treated mice displayed fewer number of avoidances than saline-treated counterparts. It was concluded that housing condition may be a useful variable in evaluating the effects of nicotine on learning tasks. Indeed, the two-way active avoidance task seems to be sensitive to housing condition. [Copyright &y& Elsevier]

The medial habenula-interpeduncular nucleus (MHb-IPN) pathway modulates negative affective states produced by nicotine withdrawal. Sex differences in the contribution of acetylcholine (ACh) systems in this pathway have not been explored. Thus, this study assessed ACh levels and gene expression of α- and β-containing nicotinic acetylcholine receptor (nAChR) subunits in the IPN of female and male rats following nicotine treatment and withdrawal. Rats were prepared with a pump that delivered nicotine for 14 days, and naïve controls received a sham surgery. In Study 1, rats were prepared with a probe in the IPN, and ACh levels were measured following saline and then mecamylamine administration. In Study 2, separate groups of naïve control or nicotine-treated rats received saline or mecamylamine and physical signs and anxiety-like behavior were assessed using elevated plus maze (EPM) procedures. The IPN was then dissected and mRNA levels were assessed using RT-qPCR methods. Nicotine treatment increased ACh levels to a larger extent in females than males. Nicotine withdrawal produced a similar increase in physical signs; however, females displayed greater anxiety-like behavior than males. In females, gene expression of α5 increased following nicotine treatment and withdrawal. In males, α7 increased following nicotine treatment and α2 and α3 increased during nicotine withdrawal. Both females and males displayed an increase in β3 and β4 during nicotine withdrawal. In females, anxiety-like behavior was correlated with α4, α5, and β2 gene expression in the IPN. These results suggest that sex differences in withdrawal are modulated via cholinergic systems in the IPN. • Following nicotine exposure, female rats displayed higher levels of ACh in the IPN than males. • Following nicotine exposure, females displayed an increase in gene expression of α5 and males an increase in α7 in the IPN. • During withdrawal, females displayed an increase in α5, β3 and β4, and males an increase in α2, α3, β3 and β4 in the IPN. • In females, the magnitude of anxiety-like behavior was correlated with the expression of α4, α5, and β2 in the IPN. [ABSTRACT FROM AUTHOR]