Nicotine Administration Impairs Sensory Gating in Long–Evans Rats

doi:10.1016/S0091-3057(98)00094-X

Pharmacology Biochemistry and Behavior

Volume 61, Issue 3, November 1998, Pages 281-289

https://doi.org/10.1016/S0091-3057(98)00094-X Get rights and content

Abstract

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.

Section snippets

Subjects

Subjects were 96 male and 96 female Long–Evans rats (Charles River Laboratories, Wilmington, MA). During the baseline phase (predrug and prehousing manipulation) all animals were individually housed in standard polypropylene shoebox cages (42 × 20.5 × 20 cm) on hardwood chip bedding (Pine-Dri). Throughout the study animals had continuous access to rodent chow (Harlan Teklad 4% Mouse/Rat Diet 7001) and water. The housing room was maintained at 23°C at 50% relative humidity on a 12-h reverse

Body Weight

Figure 1 presents the body weight data. Nicotine-treated subjects’ body weights increased less over time than did saline-treated subjects’ body weights regardless of sex or phase [during males, F(4, 172) = 37.274, p < 0.05, and females, F(4, 172) = 9.912, p < 0.05; cessation males, F(5, 210) = 17.488, p < 0.05, and females, F(5, 210) = 24.782, p < 0.05]. Grouping also decreased body weight gains over time for all subjects [during males, F(4, 172) = 3.287, p < 0.05, and females, F(4, 172) =

Discussion

The purpose of the present experiment was to examine nicotine’s effects on attention in Long–Evans rats as operationalized in the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR. In previous studies with Sprague–Dawley subjects, nicotine enhanced ASR and PPI 2, 3, 4, 5. This enhancement has been interpreted as analogous to the attentional enhancement demonstrated empirically in certain human subjects and reported by some human smokers when they smoke cigarettes. Results

Acknowledgements

The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences. This work was supported by USUHS-DoD grant RO72AR.

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Humans undergoing nicotine withdrawal showed no changes in the acoustic startle response (Kumari and Gray, 1999; Mueller et al., 1998; Postma et al., 2001). Rodent startle studies indicated conflicting results in rats (Acri et al., 1991; Faraday et al., 1999, 1998; Helton et al., 1993). Further, no effects in startle were seen after either acute nicotine administration in C57BL/6 mice (Gould et al., 2005) or during spontaneous nicotine withdrawal in C57BL/6J and DBA/2J mice (Jonkman et al., 2005; Semenova et al., 2003a).
The aversive aspects of nicotine withdrawal are powerful motivational forces contributing to the tobacco smoking habit. We evaluated measures of affective and somatic aspects of nicotine withdrawal in C57BL/6J and BALB/cByJ mice. Nicotine withdrawal was induced by termination of chronic nicotine delivery through osmotic minipumps or precipitated with the nicotinic acetylcholine receptor (nAChR) antagonists mecamylamine or dihydro-β-erythroidine (DHβE). A rate-independent discrete-trial intracranial self-stimulation threshold procedure was used to assess brain reward function. Anxiety-like behavior and sensorimotor gating were assessed in the light–dark box and prepulse inhibition (PPI) tests, respectively. Acoustic startle response and somatic signs of withdrawal were also evaluated. Spontaneous nicotine withdrawal after 14-day exposure to 10–40 mg/kg/day nicotine induced no alterations in anxiety-like behavior, startle reactivity, PPI, or somatic signs in either strain, and no changes in thresholds in C57BL/6J mice. Extended 28-day exposure to 40 mg/kg/day nicotine induced threshold elevations, increased somatic signs, and anxiety-like behavior 24 h post-nicotine in C57BL/6J mice; thresholds returned to baseline levels by day 4 in nicotine-exposed mice. Mecamylamine or DHβE administration induced threshold elevations in nicotine-exposed C57BL/6J mice compared with saline-exposed mice. In conclusion, administration of relatively high nicotine doses over prolonged periods of time induces both the affective and somatic aspects of spontaneous nicotine withdrawal in the mouse, while exposure to nicotine for shorter periods of time is sufficient for nAChR antagonist-precipitated nicotine withdrawal. The current study is one of the first to demonstrate reward deficits associated with both spontaneous and nAChR antagonist-precipitated nicotine withdrawal in C57BL/6J mice.
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Inhibitory gating is thought to be a basic process for filtering incoming stimuli to the brain. Little information is currently available concerning local neural networks of inhibitory gating or the intrinsic neurochemical substrates involved in the process.
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We found that in one subset of neurons, ketamine administration significantly reduced tone responsiveness with a subsequent loss of inhibitory gating, whereas the other subset persisted in both auditory responding and gating albeit at a weaker level. Haloperidol and nicotine had very similar effects, exemplified by a dramatic increase in the response to the initial “conditioning” tone with a subsequent improvement in inhibitory gating.
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Schizophrenic patients have deficits in prepulse inhibition (PPI) that may be alleviated by smoking/nicotine. The effect of nicotinic agents on PPI in rodents is equivocal and few studies in mice have been reported. Thus, we assessed nicotine's (0.03–1 mg/kg) effect on PPI in five mouse strains with no effects. We next determined if nicotine would reverse a phencyclidine (PCP)-induced deficit of PPI in BALB/cByJ and NMRI mice. BALB/cByJ mice have a low density of [¹²⁵I]α-bungaratoxin binding in the hippocampus and poor inhibitory gating of auditory evoked potentials (AEPs), a model related to PPI. At 1 mg/kg, nicotine selectively reversed the PCP-induced deficit of PPI in BALB/cByJ mice. The pharmacokinetic profile of nicotine (T_1/2, C_max, T_max and AUC) was identical in both strains, obviating this as a factor for the strain-dependent effect observed. Moreover, 1 mg/kg nicotine inhibited in vivo [³H]epibatidine binding with the same time-course in both strains, indicating no difference in brain “kinetics”. Since high doses of nicotine were effective in BALB/cByJ mice a role for low-affinity nicotinic receptors, e.g. α₇ receptors, is plausible. Clozapine, but not risperidone, also only reversed the PCP deficit of PPI in BALB/cByJ. Clozapine and nicotine also enhance inhibitory gating of AEPs in DBA/2 mice, and clozapine's effect is antagonized by an α₇ antagonist. Our data and previous evidence possibly suggest a role for low-affinity nicotinic receptors in the effects of clozapine and nicotine. Furthermore, BALB/cByJ mice may represent a model to test the effects of nicotinic agents acting at low-affinity nicotinic receptors.
Effect of prolonged nicotine infusion on response of rat catecholamine biosynthetic enzymes to restraint and cold stress
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There is a paradoxical relationship between nicotine and stress. To help elucidate their relationship on catecholamine biosynthesis, rats were infused with nicotine for 7–14 days before exposure to cold or restraint stress. Nicotine (5 mg/kg/day, 14 days) did not alter basal plasma corticosterone or its elevation with 24 h cold stress, but prevented corticosterone elevation following 2 h restraint stress. In adrenal medulla (AM), response of dopamine β-hydroxylase (DBH), but not tyrosine hydroxylase (TH) mRNA, to both stressors was attenuated in nicotine-infused rats. In locus coeruleus (LC), restraint stress elevated TH and DBH mRNA in saline-, but not in nicotine-infused rats. Cold stress triggered a similar response of TH and DBH mRNAs in LC with and without nicotine infusion. With shorter nicotine infusion (8 mg/kg/day, 7 days), TH mRNA in AM was not induced by restraint stress on one (1×) or two (2×) consecutive days nor was DBH mRNA in AM or LC by 2×. The findings demonstrate that constant release of nicotine can modulate, or even prevent, some stress responses at the level of the HPA axis and gene expression of catecholamine biosynthetic enzymes in LC and AM.
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Gender and genotype result in differential sensitivity to stress and to nicotine. Male and female Sprague–Dawley and Long–Evans rats exhibit different behavioral responses to immobilization stress and to chronically-administered nicotine, suggesting that these animals may be useful to model human variability in stress and nicotine sensitivity. It is possible that differences in sensitivity of the hypothalamo–pituitary–adrenocortical (HPA) axis might account for these sex and strain differences. This experiment examined corticosterone (CORT) and adrenocorticotropin hormone (ACTH) responses of male and female Sprague–Dawley (n=117) and Long–Evans (n=120) rats administered 0, 6, or 12 mg/kg/day nicotine for 14 days; half of each treatment group was exposed to immobilization stress (20 min/day). Feeding and body weight also were measured. Nicotine increased CORT and ACTH levels of Sprague–Dawley females only. Stress increased CORT and ACTH levels of all groups except for Long–Evans females. Nicotine and stress decreased feeding and body weight with greatest effects in Long–Evans females. CORT, feeding, and body weight were positively correlated among stressed females. These findings suggest that strain differences in HPA axis, body weight, and feeding responses to nicotine and to stress are robust among females but not among males. CORT reactivity and female sex hormones may explain these differences.
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This observation, which seems to contradict the wealth of evidence supporting the role of α7∗ nAChRs in attentional processes, should be tempered by the following remarks. Using the PPI paradigm, pharmacological studies performed in humans and animals have been contradictory and failed to establish the role of α7∗ nAChRs in sensory inhibition (Acri et al., 1994; Curzon et al., 1994; but see Decker et al., 1997; Faraday et al., 1998, 1999; Olivier et al., 2001). On the other hand, studies evaluating the extent of sensory inhibition by recording auditory evoked potentials have consistently reported an effect of α7 agonists or antagonists (Luntz-Leybman et al., 1992; Stevens and Wear, 1997; Stevens et al., 1998; Simosky et al., 2001).
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ArticleNicotine Administration Impairs Sensory Gating in Long–Evans Rats

Abstract

Section snippets

Subjects

Body Weight

Discussion

Acknowledgements

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Physiol. Behav.

Physiol. Behav.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Addict. Behav.

Pharmacol. Biochem. Behav.

Addict. Behav.

Behav. Ther.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Life Sci.

Biol. Psychiatry

Pharmacol. Biochem. Behav.

Pharmacol. Ther.

Nicotine modulates effects of stress on acoustic startle reflexes in ratsDependence on dose, stressor and initial reactivity

Psychopharmacology (Berlin)

Effects of nicotine on the acoustic startle reflex amplitude in rats

Psychopharmacology (Berlin)

Nicotine increases sensory gating measured as inhibition of the acoustic startle reflex in rats

Psychopharmacology (Berlin)

Evidence for sensory-selective set in young infants

Science

Cardiac and blink reflex concomitants of attentional selectivityA comparison of adults and young children

Psychophysiology

Prestimulus effects on human startle reflex in normals and schizophrenics

Psychophysiology

Circadian modulation of the rat acoustic startle response

Behav. Neurosci.

The mammalian startle response

Article
Nicotine Administration Impairs Sensory Gating in Long–Evans Rats