Adult vs. adolescent rats differ in biobehavioral responses to chronic nicotine administration.

More than 90% of smokers begin smoking during adolescence, suggesting that nicotine's actions may differ in adults vs. adolescents in ways that render adolescents vulnerable to smoking initiation. This experiment tested the hypothesis that nicotine's biobehavioral actions differ in adult and adolescent rats. Forty-two male (21 adolescents, 21 adults) and 41 female (21 adolescents, 20 adults) Sprague-Dawley rats were administered saline or 12 mg/kg/day nicotine via osmotic minipump for 21 days. Body weight, feeding, and locomotion (horizontal activity, vertical activity, center time) were measured before, during, and after saline or nicotine administration. Nicotine's effects depended on age and sex. Nicotine reduced body weight and feeding of adult males and females, and of adolescent males, but not of adolescent females. In addition, adolescent males were more sensitive than adults or adolescent females to nicotine's activity-enhancing effects. In cessation, nicotine-exposed adolescent males continued to exhibit greater activity than saline-exposed animals. Results indicate that nicotine's biobehavioral actions differ depending on age and sex.

Nicotine administration interacts with housing conditions to alter social and non-social behaviors in male and female Long-Evans rats.

Despite the fact that the anxiety-relieving effects of smoking are widely reported by smokers, human laboratory studies have not found consistent evidence for this effect. In animals, contrasting results also have been reported, with Sprague-Dawley rats unaffected by nicotine in behavioral tests of anxiety but with other rat strains (e.g., Wistar, Fischer-344) displaying behaviors indicative of anxiolysis. The present experiment used the social interaction test to evaluate effects of nicotine (12 mg/kg/day) chronically administered via minipump on social and non-social behaviors in 48 male and 48 female Long-Evans rats--a strain that has not previously been evaluated and that is known to differ from Sprague-Dawleys in other behavioral responses to nicotine. Because environmental conditions can alter behavioral effects of drugs, animals lived in either individual or same-sex group housing. Social interactions were measured on day 10 of drug administration and social behaviors (touch, follow, sniff-other, wrestle) as well as non-social behaviors (anxiety-related behaviors: freezing, grooming-self; exploratory behavior: moving) were scored. Group housing decreased social behaviors and increased anxiety-related behaviors. Nicotine's effects depended upon housing condition, such that nicotine further decreased social behaviors and increased anxiety-related behaviors of group-housed animals, with weaker effects in single-housed animals. Overall, the results suggest that nicotine's effects are modified by environmental conditions, and that nicotine administration at this dosage and in this particular rat strain results in anxiogenic effects.

The importance of acclimation in acoustic startle amplitude and pre-pulse inhibition testing of male and female rats.

The acoustic startle reflex (ASR) and pre-pulse inhibition (PPI) of the ASR are used extensively to index drug effects in rodents. Important methodological issues exist, however, with regard to the specific procedures and equipment used. In particular, the effects of acclimation to the startle procedure on response stability and the effects of testing animals in groups vs. individually have not been examined but are relevant to data interpretation. The present experiment measured acoustic startle responses with and without a pre-pulse of 25 adult Sprague-Dawley rats (12 male, 13 female) tested individually and in same-sex groups at four time points. Individual testing increased startle responses and PPI of males at time 1 and altered PPI of females at times 1, 2, and 3 compared with group testing. Responses were indistinguishable in the two testing environments at time 4. Results indicate that testing environment may affect responses when subjects have not been acclimated to the testing situation and that there are sex differences in these effects. Because responses stabilized by the fourth testing point, repeated testing of subjects particularly females, may be an important methodological inclusion when evaluating effects of drugs and other manipulations on ASR and PPI.

Effects of nicotine and stress on startle amplitude and sensory gating depend on rat strain and sex.

We recently reported that 14 days of nicotine administration (12 mg/kg/day) reduced acoustic startle reflex amplitude and impaired prepulse inhibition (PPI) of startle in male and female Long-Evans rats. These findings contrasted with reports of nicotine-induced enhancement of startle and PPI in Sprague-Dawley (a different strain) male rats. The present experiment administered 0, 6, or 12 mg/kg/day nicotine via osmotic minipump for 14 days to 120 Sprague-Dawley rats (male and female) and to 120 Long-Evans rats (male and female) and examined ASR and PPI. Half of the subjects also were stressed by immobilization once each day to examine nicotine-stress interactions. Nicotine enhanced ASR and PPI responses of Sprague-Dawley rats but impaired these responses in Long-Evans rats, regardless of sex. Effects of stress were complex and depended on strain, sex, and drug dose. These findings indicate that effects of nicotine on measures of reactivity (ASR) and sensory gating (PPI) depend on genotype and that nicotine stress interactions depend on genotype, sex, and nicotine dosage.

Effects of chronic nicotine administration on locomotion depend on rat sex and housing condition.

Nicotine's behavioral actions in the human smoker by self-report depend, in part, on the individual's gender and environment. The purpose of the present experiment was to determine whether effects of nicotine on unconditioned behaviors of rats also depend on sex and environmental conditions. Long-Evans rats (96 males and 96 females) living in individual or grouped housing were administered saline or 12 mg/kg/day nicotine via osmotic minipump for 14 days. Horizontal activity (a measure of overall activity and arousal), vertical activity (a measure of exploratory behavior), and center time (a possible index of anxiety) were measured on Day 10 of drug administration and on Day 2 of nicotine cessation. Group housing decreased horizontal and vertical activity and center time, with effects occurring sooner in females. Nicotine's effects depended on housing and sex. For males, nicotine altered indices of arousal and exploration, increasing these variables for group-housed males but decreasing them for individually housed males. For females, nicotine altered possible indices of anxiety, reducing anxiety for group-housed females. In cessation, housing effects continued in females and appeared more robustly in males. Results indicate that nicotine's chronic effects depend on subjects' sex and living environment.

Nicotine administration impairs sensory gating in Long-Evans rats.

In rats, effects of nicotine administration on sensory gating as indexed by prepulse inhibition (PPI) of the acoustic startle reflex (ASR) are unclear. We have found that nicotine administration enhances ASR and PPI in Sprague-Dawley rats, but other investigators, using Long-Evans rats, have reported no effects or enhancement of PPI only. Numerous methodological differences exist among studies in addition to subject strain, however, making it unclear whether inconsistent behavioral responses are the result of different experimental procedures or indicate a true strain difference. To investigate the role of strain in nicotine's effects on ASR and PPI, 192 male and female Long-Evans rats were administered 12 mg/kg/day nicotine via osmotic minipump for 14 days using identical methodologies employed in studies with Sprague-Dawley subjects. Effects of grouped vs. individual housing on these responses also were examined. Nicotine administration impaired ASR and PPI in Long-Evans subjects. These effects occurred in female rats regardless of housing condition, and interacted with housing in male rats. Results indicate that sex and housing are important variables in nicotine's effects. Results suggest that subject strain may be an important variable in nicotine's effects on sensory gating, and that responses of Sprague-Dawley vs. Long-Evans rats may represent a true strain difference.