Potentiated Startle As a Measure of the Negative Affective Consequences of Repeated Exposure to Nicotine in Rats

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2009 Aug 12

PMID 19669732

Citations 15

Authors

Jeffrey M Engelmann

Anna K Radke

Jonathan C Gewirtz

Affiliations

Soon will be listed here.

Abstract

Rationale: Elevated acoustic startle amplitude has been used to measure anxiety-like effects of drug withdrawal in humans and animals. Withdrawal from a single opiate administration has been shown to produce robust elevations in startle amplitude ("withdrawal-potentiated startle") that escalate in severity with repeated exposure. Although anxiety is a clinical symptom of nicotine dependence, it is currently unknown whether anxiety-like behavior is elicited during the early stages of nicotine dependence in rodents.

Objective: The objective of this study is to examine whether, as is the case with opiates, single or repeated exposure to nicotine can produce withdrawal-potentiated startle.

Methods: Rats received daily nicotine injections for 14 days, and startle amplitude was tested during spontaneous withdrawal on injection days 1, 7, and 14.

Results: Elevated startle responding was observed during nicotine withdrawal on days 7 and 14 but not on day 1, was greater at higher nicotine doses, and was reduced by a nicotine replacement injection given during an additional test session on day 15. Additional experiments demonstrated that nicotine withdrawal-potentiated startle was reduced by the alpha(2)-adrenergic agonist clonidine and that precipitated withdrawal-potentiated startle could not be induced by injection of the nicotinic acetylcholine receptor antagonist mecamylamine.

Conclusions: These results suggest that nicotine withdrawal escalates in severity across days, similar to the previously reported escalation of opiate withdrawal-potentiated startle. Potentiated startle may be a reliable measure of withdrawal from different classes of abused drugs and may be useful in the study of the early stages of drug dependence.

Citing Articles

Behavioral predictors of individual differences in opioid addiction vulnerability as measured using i.v. self-administration in rats.

Swain Y, Gewirtz J, Harris A Drug Alcohol Depend. 2021; 221:108561.

PMID: 33588371 PMC: 8048102. DOI: 10.1016/j.drugalcdep.2021.108561.

Higher anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid self-administration in rats.

Swain Y, Muelken P, Skansberg A, Lanzdorf D, Haave Z, Lesage M Psychopharmacology (Berl). 2020; 237(8):2279-2291.

PMID: 32388620 PMC: 7354901. DOI: 10.1007/s00213-020-05532-w.

Metabotropic Glutamate Receptors 2 and 3 as Targets for Treating Nicotine Addiction.

Cross A, Anthenelli R, Li X Biol Psychiatry. 2018; 83(11):947-954.

PMID: 29301614 PMC: 5953779. DOI: 10.1016/j.biopsych.2017.11.021.

Effects of age, but not sex, on elevated startle during withdrawal from acute morphine in adolescent and adult rats.

Radke A, Gewirtz J, Carroll M Behav Pharmacol. 2015; 26(5):485-8.

PMID: 26154436 PMC: 4499855. DOI: 10.1097/FBP.0000000000000151.

Anticipation of smoking sufficiently dampens stress reactivity in nicotine-deprived smokers.

Bradford D, Curtin J, Piper M J Abnorm Psychol. 2015; 124(1):128-36.

PMID: 25688439 PMC: 4332561. DOI: 10.1037/abn0000007.

References

Davis M . Sensitization of the acoustic startle reflex by footshock. Behav Neurosci. 1989; 103(3):495-503. View

Stine S, Grillon C, Morgan 3rd C, Kosten T, Charney D, Krystal J . Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine. Psychopharmacology (Berl). 2001; 154(3):274-81. DOI: 10.1007/s002130000644. View

Malin D, Lake J, Roberts L, Lanier J, Carter V, Cunningham J . Rodent model of nicotine abstinence syndrome. Pharmacol Biochem Behav. 1992; 43(3):779-84. DOI: 10.1016/0091-3057(92)90408-8. View

Solomon R, CORBIT J . An opponent-process theory of motivation. II. Cigarette addiction. J Abnorm Psychol. 1973; 81(2):158-71. DOI: 10.1037/h0034534. View

Papke R, Sanberg P, Shytle R . Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes. J Pharmacol Exp Ther. 2001; 297(2):646-56. View

Krystal J, Webb E, Grillon C, Cooney N, Casal L, Morgan 3rd C . Evidence of acoustic startle hyperreflexia in recently detoxified early onset male alcoholics: modulation by yohimbine and m-chlorophenylpiperazine (mCPP). Psychopharmacology (Berl). 1997; 131(3):207-15. DOI: 10.1007/s002130050285. View

Watkins S, Koob G, Markou A . Dramatic decreases in brain reward function during nicotine withdrawal. Nature. 1998; 393(6680):76-9. DOI: 10.1038/30001. View

Hughes J, Hatsukami D, Pickens R, Krahn D, Malin S, Luknic A . Effect of nicotine on the tobacco withdrawal syndrome. Psychopharmacology (Berl). 1984; 83(1):82-7. DOI: 10.1007/BF00427428. View

Kalinichev M, Holtzman S . Changes in urination/defecation, auditory startle response, and startle-induced ultrasonic vocalizations in rats undergoing morphine withdrawal: similarities and differences between acute and chronic dependence. J Pharmacol Exp Ther. 2003; 304(2):603-9. DOI: 10.1124/jpet.102.044206. View

10.

Jonkman S, Risbrough V, Geyer M, Markou A . Spontaneous nicotine withdrawal potentiates the effects of stress in rats. Neuropsychopharmacology. 2007; 33(9):2131-8. PMC: 2648847. DOI: 10.1038/sj.npp.1301607. View

11.

Rasmussen K, Czachura J, Kallman M, Helton D . The CCK-B antagonist LY288513 blocks the effects of nicotine withdrawal on auditory startle. Neuroreport. 1996; 7(5):1050-2. DOI: 10.1097/00001756-199604100-00019. View

12.

Saladin M, Drobes D, Coffey S, Libet J . The human startle reflex and alcohol cue reactivity: effects of early versus late abstinence. Psychol Addict Behav. 2002; 16(2):98-105. DOI: 10.1037//0893-164x.16.2.98. View

13.

Rothwell P, Thomas M, Gewirtz J . Distinct profiles of anxiety and dysphoria during spontaneous withdrawal from acute morphine exposure. Neuropsychopharmacology. 2009; 34(10):2285-95. PMC: 2726902. DOI: 10.1038/npp.2009.56. View

14.

Piasecki T, Niaura R, Shadel W, Abrams D, Goldstein M, Fiore M . Smoking withdrawal dynamics in unaided quitters. J Abnorm Psychol. 2000; 109(1):74-86. DOI: 10.1037//0021-843x.109.1.74. View

15.

Ise Y, Narita M, Nagase H, Suzuki T . Modulation of kappa-opioidergic systems on mecamylamine-precipitated nicotine-withdrawal aversion in rats. Neurosci Lett. 2002; 323(2):164-6. DOI: 10.1016/s0304-3940(02)00074-5. View

16.

Malin D, Lake J, Short P, Blossman J, Lawless B, Schopen C . Nicotine abstinence syndrome precipitated by an analog of neuropeptide FF. Pharmacol Biochem Behav. 1996; 54(3):581-5. DOI: 10.1016/0091-3057(95)02279-1. View

17.

Acri J, Brown K, Saah M, Grunberg N . Strain and age differences in acoustic startle responses and effects of nicotine in rats. Pharmacol Biochem Behav. 1995; 50(2):191-8. DOI: 10.1016/0091-3057(94)00285-q. View

18.

Malin D, Lake J, Carter V, Cunningham J, Wilson O . Naloxone precipitates nicotine abstinence syndrome in the rat. Psychopharmacology (Berl). 1993; 112(2-3):339-42. DOI: 10.1007/BF02244930. View

19.

Bozarth M, Pudiak C, KuoLee R . Effect of chronic nicotine on brain stimulation reward. I. Effect of daily injections. Behav Brain Res. 1998; 96(1-2):185-8. DOI: 10.1016/s0166-4328(98)00050-3. View

20.

Glassman A, Jackson W, Walsh B, Roose S, Rosenfeld B . Cigarette craving, smoking withdrawal, and clonidine. Science. 1984; 226(4676):864-6. DOI: 10.1126/science.6387913. View