Adolescent rats were more vulnerable than adults to lasting memory deficits from a cannabinoid
Chronic cannabinoid exposure during adolescence, but not adulthood, produced lasting spatial memory deficits in rats that correlated with reduced new brain cell growth in the hippocampus.
Quick Facts
What This Study Found
Researchers administered the synthetic cannabinoid WIN55,212-2 to adolescent rats (starting at postnatal day 27-30) and adult rats (starting at postnatal day 54-57) for 20 consecutive days, followed by a 20-day drug-free washout period. After washout, adolescent-treated rats showed significant deficits in spatial learning and memory in the Morris water maze test, while adult-treated rats did not.
The cognitive deficits in adolescent rats correlated with decreased numbers of newly generated neurons in the dorsal hippocampus, a brain region critical for spatial memory. Both age groups showed increased thigmotaxis (wall-hugging behavior in the maze) early in training, but only the adolescent group showed persistent learning and memory problems.
Key Numbers
Twenty days of daily cannabinoid exposure followed by 20-day washout. Adolescent exposure started at postnatal day 27-30. Adult exposure started at postnatal day 54-57. Dose: 1 mg/kg WIN55,212-2 daily. Spatial memory deficits appeared only in the adolescent group.
How They Did This
Adolescent and adult Wistar rats received daily injections of WIN55,212-2 (1 mg/kg) or vehicle for 20 days, followed by a 20-day washout. Cognitive function was assessed using the Morris water maze and two-way active avoidance tests. Hippocampal neurogenesis was quantified using doublecortin immunostaining.
Why This Research Matters
This study provided mechanistic evidence for why the adolescent brain may be particularly vulnerable to cannabis. By showing that reduced hippocampal neurogenesis correlated with cognitive deficits only in adolescent-exposed animals, it linked brain development disruption to functional outcomes.
The Bigger Picture
Epidemiological studies have consistently linked adolescent cannabis use to cognitive outcomes, but human studies cannot establish causation due to confounding factors. Animal studies like this one provide the controlled experimental evidence needed to demonstrate a causal effect of cannabinoid exposure on the developing brain.
What This Study Doesn't Tell Us
WIN55,212-2 is a synthetic cannabinoid that differs from THC in potency and receptor selectivity. The dose and administration route (daily injection) do not mirror typical human cannabis use. Rat adolescence and human adolescence are not directly equivalent. Only spatial memory and one measure of neurogenesis were assessed.
Questions This Raises
- ?Would THC itself produce the same age-dependent pattern?
- ?Are there interventions that could restore hippocampal neurogenesis after adolescent cannabinoid exposure?
- ?Is there a critical window within adolescence that is most vulnerable?
Trust & Context
- Key Stat:
- Adolescent-exposed rats showed lasting memory deficits; adult-exposed rats did not
- Evidence Grade:
- Controlled animal experiment with appropriate comparison groups, but uses a synthetic cannabinoid rather than THC and findings require cautious translation to humans.
- Study Age:
- Published in 2014.
- Original Title:
- Chronic exposure to WIN55,212-2 affects more potently spatial learning and memory in adolescents than in adult rats via a negative action on dorsal hippocampal neurogenesis.
- Published In:
- Pharmacology, biochemistry, and behavior, 120, 95-102 (2014)
- Authors:
- Abboussi, Oualid(4), Tazi, Abdelouahhab, Paizanis, Eleni, El Ganouni, Soumaya
- Database ID:
- RTHC-00757
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Why might adolescent brains be more affected by cannabis?
This animal study found that cannabinoid exposure during adolescence reduced the generation of new neurons in the hippocampus, a brain region still developing during adolescence. Adult brains, with more mature hippocampal development, were not similarly affected.
Did the memory problems go away after stopping the drug?
No. After a 20-day drug-free washout period, the adolescent-exposed rats still showed spatial memory deficits and reduced hippocampal neurogenesis, suggesting lasting effects.
Read More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-00757APA
Abboussi, Oualid; Tazi, Abdelouahhab; Paizanis, Eleni; El Ganouni, Soumaya. (2014). Chronic exposure to WIN55,212-2 affects more potently spatial learning and memory in adolescents than in adult rats via a negative action on dorsal hippocampal neurogenesis.. Pharmacology, biochemistry, and behavior, 120, 95-102. https://doi.org/10.1016/j.pbb.2014.02.014
MLA
Abboussi, Oualid, et al. "Chronic exposure to WIN55,212-2 affects more potently spatial learning and memory in adolescents than in adult rats via a negative action on dorsal hippocampal neurogenesis.." Pharmacology, 2014. https://doi.org/10.1016/j.pbb.2014.02.014
RethinkTHC
RethinkTHC Research Database. "Chronic exposure to WIN55,212-2 affects more potently spatia..." RTHC-00757. Retrieved from https://rethinkthc.com/research/abboussi-2014-chronic-exposure-to-win552122
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.