The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity.

1. The effects of acute and subchronic nicotine and (+)-amphetamine on the extracellular levels of dopamine and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in nucleus accumbens (NAc) have been studied in conscious, freely-moving rats by use of in vivo microdialysis. 2. In rats which had been habituated to the test apparatus for approximately 80 min, the acute subcutaneous (s.c.) administration of nicotine (0.1 or 0.4 mg kg-1) caused a dose-dependent increase (P less than 0.01) in spontaneous activity and evoked significant increases (P less than 0.05) in the extracellular levels of DOPAC and HVA. 3. Measurements made 24 h after the last injection of nicotine showed that pretreatment with the higher doses tested (0.4 mg kg-1) resulted in increased basal levels of dopamine (P less than 0.01) and decreased basal levels of DOPAC (P less than 0.05) in the NAc dialysates. 4. Pretreatment with nicotine (0.1 or 0.4 mg kg-1 daily for 5 days) enhanced the effects of the drug on spontaneous locomotor activity and enhanced the effects of the drug on extracellular levels of dopamine to the extent that the response became significant (P less than 0.05). 5. If a dopamine uptake inhibitor, nomifensine, was added to the Ringer solution used to dialyse the probe, the s.c. administration of both acute and subchronic nicotine (0.4 mg kg-1) resulted in significant increases (P less than 0.05) in the dopamine concentration in the dialysate. Under these conditions, pretreatment with nicotine prior to the test day prolonged (P less than 0.05) the dopamine response to a challenge dose of nicotine.6. Subcutaneous injections of (+)-amphetamine (0.2 or 0.5 mg kg-') evoked dose-dependent increases in both spontaneous activity and the concentration of dopamine in NAc dialysates. These responses were unaffected by 5 days pretreatment with the drug.7. The results of this study support the conclusion that the enhanced locomotor response to nicotine observed in animals pretreated with the drug prior to the test day is associated with potentiation of its effects on dopamine secretion in the NAc.