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Behavioural and neurochemical adaptations to nicotine in rats: influence of NMDA antagonists
Author(s) -
Shoaib M.,
Benwell M.E.M.,
Akbar M.T.,
Stolerman I.P.,
Balfour D.J.K.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14854.x
Subject(s) - nicotine , dizocilpine , pharmacology , nmda receptor , nucleus accumbens , neurochemical , chemistry , sensitization , dopamine , stimulant , antagonist , medicine , receptor , neuroscience , psychology , biochemistry
1 The repeated co‐administration of the non‐competitive N‐methyl‐ d ‐aspartate (NMDA) receptor antagonist dizocilpine (0.1 and 0.3 mg kg −1 , i.p.) with nicotine (0.4 mg kg −1 , s.c.) attenuated the development of tolerance to the locomotor depressant effect of the nicotine in rats. 2 The repeated co‐administration of the competitive NMDA antagonist d ‐CPPene (SDZ EAA 494; 3‐(2‐carboxypiperazin‐4‐yl)‐1‐propenyl‐1‐phosphonic acid, 2 and 8 mg kg −1 , i.p.) also attenuated tolerance to the locomotor depressant effect of nicotine. 3 Dizocilpine (0.3 mg kg −1 , i.p.) pretreatment attenuated sensitization to the locomotor stimulant effect of nicotine (0.4 mg kg −1 , s.c.) and prevented sensitization of nicotine‐induced dopamine release in the nucleus accumbens. However, pretreatment with dizocilpine alone caused a modest enhancement of the behavioural response to a subsequent acute dose of nicotine. 4 d ‐CPPene (2.0 mg kg −1 , i.p.) pretreatment prevented sensitization to the nicotine‐induced dopamine release in the nucleus accumbens. There was no enhanced locomotor response that could be attributed to nicotine pretreatment when d ‐CPPene was co‐administered with nicotine. However, pretreatment with d ‐CPPene alone enhanced the locomotor response to an acute dose of nicotine. 5 The results suggest the involvement of NMDA receptors in adaptations of the behavioural and neurochemical effects of nicotine that occur as a result of repeated administration of the drug.