Behavioural and neurochemical adaptations to nicotine in rats: influence of NMDA antagonists

Abstract

1 The repeated co-administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (0.1 and 0.3 mg kg-, i.p.) with nicotine (0.4 mg kg-', 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-', i.p.) also attenuated tolerance to the locomotor depressant effect of nicotine. 3 Dizocilpine (0.3 mg kg-',i.p.) pretreatment attenuated sensitization to the locomotor stimulant effect of nicotine (0.4 mg kg-', 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-', 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.

Neurochemical and behavioural interactions between ibogaine and nicotine in the rat

“…The mesolimbic dopamine response to nicotine can be completely inhibited by a desensitizing dose of nicotine, while a residual level of nicotine-evoked locomotion persists (Benwell et al, 1995). Moreover, the competitive NMDA antagonist, 3-(2-carboxypiperazin -4 -yl) -1 -propenyl -1 -phosphoric acid (CPPene), also appears to be able to inhibit the NAc dopamine response to nicotine while the locomotor response to the drug is unaffected (Shoaib et al, 1994). These data are clearly difficult to reconcile with the hypothesis that the locomotor stimulant response to nicotine always corresponds closely with its effects on dopamine overflow in the extracellular space of the NAc.…”

Mecamylamine but not the α7 receptor antagonist α‐bungarotoxin blocks sensitization to the locomotor stimulant effects of nicotine

“…Moreover, sensitization to enhanced mesolimbic dopamine secretion after repeated nicotine administration has been associated with locomotor sensitization (Benwell & Balfour, 1992). In addition, nicotine-induced sensitization of nucleus accumbens dopamine secretion appears to depend upon costimulation of NMDA receptors although the role of glutamate receptors in the expression of locomotor sensitization appears more complex (Shoaib et al, 1994;Balfour et al, 1998).…”

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

“…Blockade of N-methyl-D-aspartate receptors using MK-801, a non-competitive channel blocker (Amador and Dani, 1991, Halliwell et al, 1989, Huettner and Bean, 1988and Wong et al, 1986) inhibited nicotine-induced dopamine release in the nucleus accumbens (Szirá-ki et al, 1998). MK-801 also attenuated development and expression of nicotine-induced behavioral sensitization and the development of tolerance to the locomotor depressant effects of nicotine (Shim et al, 2002, Shoaib et al, 1994a, Shoaib et al, 1994b, Shoaib et al, 1997and Shoaib and Stolerman, 1992. Due to the apparent role of N-methyl-D-aspartate receptors in modulation of behavioral effects of nicotine, we used MK-801 to determine if N-methyl-D-aspartate receptor activation is involved in nicotine's ability to serve as a conditional stimulus.…”

“…For example, repeated pairings of a conditional stimulus such as a chamber or fl avor with a nicotine unconditioned stimulus can produce a place preference (Fudala et al, 1985, Shoaib et al, 1994aand Shoaib et al, 1994b, taste aversion Williamson, 1984 andKumar et al, 1983), or conditioned hyperactivity (Bevins and Palmatier, 2003, Bevins et al, 2001, Shoaib et al, 1994a, Shoaib et al, 1994band Walter and Kuschinsky, 1989 in rats. More recently, systemic nicotine has been found to serve as a positive drug feature (occasion setter) indicating when a discrete light conditional stimulus will be followed by brief access to liquid sucrose and Palmatier et al, 2005.…”