SSRIs and SNRIs Antagonize the Conditional Stimulus Effects of Nicotine

Neuropharmacology of the Interoceptive Stimulus Properties of Nicotine

“…Based on initial findings that two bAPi analogs ( N,N’ -decane-1,10-diyl- bis -picolinium diiodide, bPiDI; and N,N’ -dodecane-1,12-diyl- bis -picolinium dibromide, bPiDDB) attenuate nicotine-evoked DA release in nucleus accumbens and nicotine self-administration [72–74], each of the bAPi analogs has been tested for blockade of nicotine discrimination. Although several bAPi analogs selectively inhibit nicotine-induced hyperactivity, none block the S D or CS effects of nicotine [21, 75]. Thus, it appears that while α6β2* nAChRs play a critical role in the DA-mediated reinforcing and stimulant properties of nicotine, this subtype does not seem to be important for the interoceptive stimulus effects of nicotine.…”

“…The N -methyl-D-aspartate (NMDA) glutamate receptor and α3β4 nAChR antagonist dextromethorphan (DXM) also fails to substitute for or alter the S D effects of nicotine [76, 77]. However, DXM partially blocks the CS, and fully blocks the locomotor, effects of nicotine [75]. This antagonism may be mediated by DXM antagonism of NMDA receptors, rather than α3β4* nAChRs, given that pretreatment with MK-801, a noncompetitive NMDA receptor antagonist, fully blocks the CS effects of nicotine [30; see later].…”

“…In substitution tests, the α7 agonists GTS-21 and WO 01/60821A1 do not substitute for nicotine in rats [56, 78]. In interaction tests, GTS-21 and the α7 antagonist methyllycaconitine (MLA) fail to alter the stimulus effects of nicotine in rats [50, 64, 75, 79, 80]. However, a recent study demonstrated that nicotine substitutes more readily in WT mice than in α7 KO mice trained to discriminate d -amphetamine, and that MLA attenuates the S D effects of nicotine in nicotine-trained WT mice, as well as the S D effects of nicotine and d -amphetamine in WT mice trained to discriminate d -amphetamine [19].…”