Hyperactivity Induced By Vapor Inhalation of Nicotine in Male and Female Rats

Area of Science:

• Pharmacology
• Neuroscience
• Toxicology

Background:

• Preclinical models for electronic nicotine delivery systems (ENDS) are scarce, necessitating the development of experimental approaches to assess their effects.
• Understanding the impact of inhaled nicotine, particularly concerning sex-based differences, is crucial for comprehensive risk assessment.

Approach:

• Male and female Wistar rats were exposed to propylene glycol vehicle, nicotine (NIC) vapor, or subcutaneous NIC injection.
• Changes in body temperature and locomotor activity were measured, with mecamylamine used to confirm pharmacological specificity.
• Plasma nicotine and cotinine levels were quantified following both inhalation and injection routes.

Key Points:

• Nicotine inhalation significantly increased locomotor activity in female rats, an effect blocked by mecamylamine.
• Similar hyperlocomotion was observed following subcutaneous NIC administration.
• Male rats exhibited increased activity with extended or repeated nicotine inhalation, while their body temperature remained unaffected.

Conclusions:

• Nicotine inhalation effectively increases locomotor activity in both sexes, comparable to or exceeding subcutaneous injection.
• Observed sex differences in response may be attributed to variations in plasma nicotine levels, baseline activity, or vehicle response.
• This study provides a validated preclinical model for evaluating ENDS effects, highlighting important sex-specific considerations.