THE EFFECTS OF ACUTE AND REPEATED NICOTINE TREATMENT ON NUCLEUS-ACCUMBENS DOPAMINE AND LOCOMOTOR-ACTIVITY

Citation
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
Citations number
38
Language
INGLESE
art.tipo
Article
ISSN journal
0007-1188
Volume
105
Issue
4
Year of publication
1992
Pages
849 - 856
Database
ISI
SICI code
0007-1188(1992)105:4<849:TEOAAR>2.0.ZU;2-O
Abstract
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.