Mem. Benwell et Djk. Balfour, THE EFFECTS OF ACUTE AND REPEATED NICOTINE TREATMENT ON NUCLEUS-ACCUMBENS DOPAMINE AND LOCOMOTOR-ACTIVITY, British Journal of Pharmacology, 105(4), 1992, pp. 849-856
1 The effects of acute and subchronic nicotine and (+)-amphetamine on
the extracellular levels of dopamine and its metabolites, dihydroxyphe
nylacetic acid (DOPAC) and homovanillic acid (HVA) in nucleus accumben
s (NAc) have been studied in conscious, freely-moving rats by use of i
n vivo microdialysis. 2 In rats which had been habituated to the test
apparatus for approximately 80 min, the acute subcutaneous (s.c.) admi
nistration of nicotine (0.1 or 0.4 mg kg-1) caused a dose-dependent in
crease (P < 0.01) in spontaneous activity and evoked significant incre
ases (P < 0.05) in the extracellular levels of DOPAC and HVA. 3 Measur
ements made 24 h after the last injection of nicotine showed that pret
reatment with the higher doses tested (0.4 mg kg-1) resulted in increa
sed basal levels of dopamine (P < 0.01) and decreased basal levels of
DOPAC (P < 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 b
ecame significant (P < 0.05). 5 If a dopamine uptake inhibitor, nomife
nsine, 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 < 0.05) in the dopamine concen
tration in the dialysate. Under these conditions, pretreatment with ni
cotine prior to the test day prolonged (P < 0.05) the dopamine respons
e to a challenge dose of nicotine. 6 Subcutaneous injections of (+)-am
phetamine (0.2 or 0.5 mg kg-1) evoked dose-dependent increases in both
spontaneous activity and the concentration of dopamine in NAc dialysa
tes. These responses were unaffected by 5 days pretreatment with the d
rug. 7 The results of this study support the conclusion that the enhan
ced 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.