Short CommunicationA two-injection protocol for nicotine sensitization

- A two-injection protocol of nicotine exposure resulted in significant nicotine sensitization.
- Mecamylamine blocked the development of nicotine sensitization using a two-injection protocol.
- Two-injection nicotine sensitization was context-independent.

Sensitization to the locomotor activating effect of drugs of abuse occurs following repeated exposure to a drug, and/or when limited exposure to a drug is paired with a specific environment. Conditioned, or context-dependent, sensitization has been well-characterized using limited exposure protocols in, for example, cocaine- and amphetamine-treated animals. However, little data exists regarding limited exposure protocols for other drugs of abuse, such as nicotine. The current experiment investigated whether a two-injection protocol of nicotine administration would result in locomotor sensitization. Mice administered two injections of nicotine (0.175 mg/kg, s.c.) 7 d apart demonstrated significant locomotor sensitization in response to the second exposure. Furthermore, the development of this sensitization was blocked by the administration of the nicotinic acetylcholine receptor antagonist mecamylamine (2 mg/kg) prior to the first nicotine exposure. In a follow-up study, we found that this two-injection nicotine sensitization was independent of context, as separate groups of mice given an initial nicotine exposure (0.175 mg/kg, s.c.) in either the specific environment in which locomotor activity was tested or in their home cages demonstrated equivalent levels of locomotor activity during subsequent testing 7 d later. These data suggest a novel approach to nicotine sensitization using limited nicotine exposure.