Nicotine as a discriminative stimulus in rats depleted of norepinephrine or 5-hydroxytryptamine.

Rats were trained to make a specific behavioral response in a T-maze apparatus conditional upon whether they were injected with 0.4 mg/kg nicotine or saline. Depletion of brain levels of 5-hydroxytryptamine by orally administered para-chlorophenylalanine had no significant effect on the rats' ability to discriminate nicotine. However, both insoluble alpha-methyl-p-tyrosine and its ester, at intraperitoneal doses of 90 and 135 mg/kg, respectively, significantly decreased discrimination of nicotine at 180 and 270 min post-administration. At these doses and times, saline discrimination was not altered. The experimental evidence indicates that nicotine's CNS cueing effect is mediated by norepinephrine, and this is discussed in light of the Burn and Rand hypothesis. It is proposed that, nicotine may act on a specific nicotine-sensitive cholinergic receptor in the CNS, which causes release of norepinephrine which, in turn, produces the interoceptive cueing effect that enables the rats to make the appropriate behavioral response. [ABSTRACT FROM AUTHOR]