Effects of chronic nicotine, nicotine withdrawal and subsequent nicotine challenges on behavioural inhibition in rats.

RATIONALE

Drug addiction is a chronically relapsing disorder characterised by compulsive drug use and loss of control over drug intake. Although several theories propose impulsivity as a key component of addiction, the precise nature of this relationship remains unclear.

OBJECTIVES

This study aims to investigate the short- and longer-term effects of chronic nicotine administration on behavioural inhibition.

METHODS

Rats were trained on a symmetrically reinforced go/no-go task, following which they were subcutaneously prepared with osmotic minipumps delivering either nicotine (3.16 mg kg(-1) day(-1) (freebase)) or saline for 7 days. Performance was assessed daily during chronic treatment, in early and late abstinence, and in response to acute nicotine challenges following prolonged abstinence.

RESULTS

Chronic nicotine resulted in a transient reduction in inhibitory control. Spontaneous withdrawal was associated with a nicotine abstinence syndrome, the early stages of which were characterised by a significant increase in inhibitory control. This was, however, short-lived with a decrease in inhibition observed in the second week of abstinence. Whilst performance returned to baseline by the end of the third week, acute challenges (0.125, 0.25, 0.5 mg/kg, SC) revealed that nicotine exposure had sensitised animals to the disinhibitory effects of the compound.

CONCLUSIONS

Drug-induced loss of inhibitory control may be critically involved both in the initial and later stages of addiction. Neuroadaptations occurring during chronic exposure to and/or withdrawal from nicotine render animals more sensitive to the disinhibitory effects of the drug. Longer-term changes in behaviour may play an important role in the increased susceptibility to relapse in those with a history of nicotine abuse.