Low dopamine levels during withdrawal tempt smokers to relapse
MedWire News: The low dopamine levels found in smokers attempting to "kick the habit" may promote relapse, say researchers.
Dopamine is a neurotransmitter involved in various brain-signaling pathways, including those associated with drug sensitivity. The authors of this study, published in Biological Psychiatry, explain that changes in dopamine levels are thought to correlate with the symptoms of withdrawal from chronic nicotine exposure.
John Dani and colleagues, from the Baylor College of Medicine in Houston, Texas, USA, tested this theory by characterizing changes in dopamine levels with nicotine withdrawal. They studied mice that had been administered nicotine in their drinking water for 4 to 12 weeks before the nicotine was then withheld for a further 1 to 10 days, simulating withdrawal.
The research team measured dopamine levels in the mice using microdialysis or fast-scan cyclic voltammetry. They found that the dopamine levels decreased upon withdrawal of nicotine, and that the length of time that this low basal dopamine state lasted depended on the length of nicotine treatment.
The mean basal dopamine level after 1 day of withdrawal was significantly lower after 4 weeks and 12 weeks of nicotine treatment compared with the control group (0.22 and 0.24 vs 0.31 nmol/L, respectively). The researchers also found that this "hypodopaminergic state" could be reversed by administering an acute dose of nicotine (1 mg/kg intraperitoneal injection) after 1 day of withdrawal.
The researchers also analyzed tonic (approximately 3 Hz) and phasic burst (approximately 20 Hz) dopamine firing patterns using fast-scan cyclic voltammetry, and found that the dopamine levels associated with both types of signaling activity were reduced during nicotine withdrawal. However, the tonic dopamine signals and the basal dopamine concentration were found to be disproportionately lower than the phasic dopamine signals, meaning that tonic dopamine release was more strongly inhibited than phasic release during withdrawal.
"These findings have implications for understanding how exposure to drug-associated cue or drug relapse might act upon and exploit existing pathological changes in [dopamine] function arising from long term nicotine use," conclude Dani and team. "Future therapies aimed at restoring low tonic [dopamine] levels might represent an important therapeutic target for the treatment of nicotine addiction."
"This study is an elegant example of yet another way that addiction 'hijacks' the reward system. The phasic release of dopamine triggers us to seek things that, in theory, help us to adapt to our environment," commented John Krystal, Editor of Biological Psychiatry, in a press release. "However, in addiction the phasic release of dopamine is heightened and it triggers the pursuit of abused substances. This disturbance of dopamine function would, conceivably, make it that much harder to avoid seeking drugs of abuse."
By Chloe McIvor