Potentiated startle as a measure of the negative affective consequences of repeated exposure to nicotine in rats.
BACKGROUND
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.
Engelmann
Jeffrey M
JM
Department of Psychology, University of Minnesota, 75 East River Rd, Minneapolis, MN 55455, USA.
Radke
Anna K
AK
Gewirtz
Jonathan C
JC
D000161:Acoustic Stimulation / Q000379:methods; D000700:Analgesics / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology / Q000627:therapeutic use; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D013997:Time Factors; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*
D000700:Analgesics; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine; D003000:Clonidine