The effects of chronic versus acute desipramine on nicotine withdrawal and nicotine self-administration in the rat.
BACKGROUND
Nicotine withdrawal is characterized by depression-like symptomatology that may be mediated by dysregulations in norepinephrine transmission. These aversive aspects of nicotine withdrawal and the rewarding effects of nicotine play major roles in maintaining nicotine dependence.


OBJECTIVE
The aim of this work was to evaluate the effects of desipramine (DMI), a preferential norepinephrine reuptake inhibitor and antidepressant, on preclinical models of nicotine dependence in rats.


METHODS
A rate-independent current-intensity discrete-trial threshold intracranial self-stimulation procedure was used to assess brain reward function during nicotine withdrawal induced by cessation of nicotine infusion via subcutaneous osmotic mini pumps (3.16 mg/kg/day, base). Nicotine withdrawal was also measured by somatic signs of withdrawal. DMI was administered acutely (2 or 5 mg/kg, salt) during nicotine/saline withdrawal. In other naïve rats, chronic DMI treatment via mini pump (15 mg/kg/day, salt) began after 7 days of nicotine/saline exposure and continued during administration of nicotine/saline for 14 days and during nicotine/saline withdrawal. Additional rats acquired intravenous nicotine- or food-maintained responding, were prepared with DMI/vehicle-containing mini pumps, and self-administered nicotine or food during 12 days of DMI/vehicle exposure.


RESULTS
Acute DMI administration had no effect on threshold elevations observed in nicotine-withdrawing rats. Chronic DMI administration prevented the reward threshold elevations and the increased somatic signs of nicotine withdrawal. Although chronic DMI significantly decreased nicotine self-administration, it also decreased food-maintained responding.


CONCLUSIONS
The results suggest that norepinephrine reuptake inhibitors may be effective anti-smoking treatments that reduce the anhedonic depression-like and somatic components of nicotine withdrawal and may alter the rewarding effects of nicotine and food.
Paterson
Neil E
NE
Department of Psychiatry, Semel Institute for Neuroscience & Human Behavior, University of California at Los Angeles, Los Angeles, CA 90095-1563, USA.
Semenova
Svetlana
S
Markou
Athina
A
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003216:Conditioning, Operant / Q000187:drug effects; D003863:Depression / Q000523:psychology; D003891:Desipramine / Q000627:therapeutic use*; D005502:Food; D015918:Infusion Pumps, Implantable; D007275:Injections, Intravenous; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012201:Reward; D012646:Self Administration; D012653:Self Stimulation; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology*; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000523:psychology
D000929:Antidepressive Agents, Tricyclic; D018722:Nicotinic Agonists; D009538:Nicotine; D003891:Desipramine