Tolerance but No Spontaneous Withdrawal Following Repeated THC Injections in Male and Female Rats

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• Prolonged cannabis use can lead to tolerance and dependence.
• Limited animal research exists on spontaneous withdrawal from delta-9-tetrahydrocannabinol (THC).
• Previous studies used high THC doses, reporting mild withdrawal symptoms.

Purpose of the Study:

• To investigate the magnitude and duration of spontaneous THC withdrawal in male and female rats.
• To utilize voluntary home cage wheel running as a measure of withdrawal.
• To assess tolerance development to THC.

Main Methods:

• Male and female Sprague-Dawley rats received daily THC (3 mg/kg, s.c.) or vehicle injections for 7 days.
• Tolerance was assessed on day 8 with a THC injection.
• Spontaneous withdrawal was monitored for 5 days post-treatment using wheel running activity.

Main Results:

• THC significantly decreased wheel running in both sexes, indicating acute effects.
• Tolerance to THC's effects on wheel running developed by day 8.
• No significant changes in wheel running were observed during spontaneous THC withdrawal.
• No sex differences were found in THC effects or tolerance development.

Conclusions:

• Spontaneous THC withdrawal in rats appears to be mild, even with developed tolerance and acute locomotor suppression.
• The lack of significant withdrawal symptoms contrasts with the pronounced effects seen in opioid withdrawal models.
• Home cage wheel running is a sensitive measure for assessing withdrawal phenomena in preclinical studies.