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

Abstract

Cigarette smokers report that one reason for smoking is that smoking helps them cope with stress, but there is conflicting evidence as to whether nicotine reduces physiological and behavioral responses to stress. The acoustic startle reflex amplitude, pre-pulse inhibition, and habituation of the reflex provide quantifiable measures of behavioral reactivity that may be sensitive to stress-induced changes that are altered by nicotine. In the present experiment, rats classified as high and low reactors according to baseline startle amplitudes were administered nicotine (6 or 12 mg/kg/day) or saline by osmotic minipump for 11 days. On day 11, animals were acutely stressed by restraint or observation of restraint of conspecifics prior to startle measurement. Nicotine and stress each independently increased acoustic startle amplitude and amount of pre-pulse inhibition, but in combination, the effect of restraint stress and 12 mg/kg nicotine were indistinguishable from saline-treated, non-stressed controls. In contrast, the 6 mg/kg nicotine dose enhanced effects of both restraint and observation stressors on startle amplitude and pre-pulse inhibition. Animals classified as highly reactive prior to treatment were more responsive to nicotine, stress, and the combination, suggesting that initial reactivity is an important determinant of drug and stress effects. Results indicate that nicotine can both reduce and enhance stress effects on reflex amplitude and pre-pulse inhibition depending upon nicotine dose, stressor, and individual differences in reactivity.

Nicotine Effect on Prepulse Inhibition and Prepulse Facilitation in Schizophrenia Patients

“…Animal studies have shown that nicotine enhances acoustic PPI in some rodent strains (Acri, 1994;Curzon et al, 1994;Acri et al, 1995;Faraday et al, 1999;Schreiber et al, 2002;Spielewoy and Markou, 2004); an effect thought to be mediated by nicotinic acetylcholine receptors (nAChRs) (Schreiber et al, 2002;Suemaru et al, 2004). However, other studies have shown no effect, or even the opposite effect (Decker et al, 1997;Faraday et al, 1999;Mirza et al, 2000;Schreiber et al, 2002).…”

Effects of Nicotine Administration and Stress on Sensory-Gating Depend on Rat Strain and Sex

“…2) The Acoustic Startle Reflex and Pre-Pulse Inhibition: Behavioral Indices of Attention Changes in attentional processes as a result of nicotine administration also have been reported in rats as measured by the acoustic startle reflex (ASR) and pre-pulse inhibition paradigm (Acri, Morse, & Grunberg, 1991;Acri, 1992;Helton, Modlin, Tizzano, & Rasmussen, 1993;Acri, Morse, Papke, & Grunberg, 1994;Acri, 1994;CUTZon, Kim, & Decker, 1994;Acri, Brown, Saah, & Grunberg, 1995;Rasmussen, Czachura, Kallman, & Helton, 1996). The ASR and prepulse inhibition of the ASR are behavioral responses believed to index central processes related to information processing (Swerdlow, Caine, Braff, & Geyer, 1992) and possibly attention CAcri et al, 1991;Acri, 1992Acri, , 1994Acri et al, 1994;Popke et aI., 1994;Acri et aI., 1995).…”

“…Specifically, in empirical studies, nicotine administration decreased body weight in humans and rats (Grunberg, 1982;Winders & Grunberg, 1989), decreased aggression in humans (Cherek, 1981;Cherek et aI., 1991) and in rats (Silvennan, 1971;ScheufeJe, 1997), and altered biochemical and behavioral responses to stress in rats (Benwell & Balfour, 1982;Cam & Bassett, 1983;1984;Sharp, Beyer, Levine, Morley, & McAllen. 1987;Peck, Dilsaver, & McGee, 1991;Acri, 1992Acri, , 1994Takada, Thara, Vrano, & Takada, 1995) and in humans (MacDougall, Musante, Castillo, & Acevedo, 1988;Gilbert, Robinson, Chamberlin, & Spielberger, 1989;Pomerleau & Pomerleau, 1990;Levin, Rose, Behm, & Caskey, 1991;Smits, Temme, & Thien, 1993).…”

“…The ASR and prepulse inhibition of the ASR are behavioral responses believed to index central processes related to information processing (Swerdlow, Caine, Braff, & Geyer, 1992) and possibly attention CAcri et al, 1991;Acri, 1992Acri, , 1994Acri et al, 1994;Popke et aI., 1994;Acri et aI., 1995). The acoustic startle reflex is a characteristic sequence of involuntary, muscular responses elicited by a sudden, intense acoustic stimulus (Davis, 1984).…”

“…Pre-pulse inhibition is believed to index an innate sensory~cognitive-motor Ugating" mechanism that operates at a non-volitional level 15 and underlies the organism's ability to select relevant stimuli from the environment while screening out irrelevant information (Swerdlow, Caine, Braff, & Geyer, 1992). PPI also has been interpreted to reflect processes associated with attention (Acri et al, 1991;Acri, 1992Acri, , 1994Acri et al, 1994;Grunberg et al, 1994;, and in humans PPI is negatively correlated with distractibility (Karper et al, 1996). Because the ASR-PPI paradigm indexes substrates believed to underlie information-processing and attention, use of this procedure avoids the complications of task choice.…”