Effects of perinatal exposure to delta-9-tetrahydrocannabinol on the emotional reactivity of the offspring: a longitudinal behavioral study in Wistar rats.
BACKGROUND
The endocannabinoid system plays a crucial role in the control of emotionality and recent clinical findings have shown that heavy prenatal exposure to cannabis is significantly associated with self-reported anxiety symptoms in exposed children. However, the long-term neurobehavioral consequences of in utero exposure to low-moderate doses of cannabinoid compounds have never been investigated.


OBJECTIVE
The objective of this study was to investigate whether perinatal exposure to moderate doses of the active constituent of cannabis, the CB(1) cannabinoid receptor agonist delta-9-tetrahydrocannabinol (THC), influences the emotional reactivity of rat offspring.


METHODS
Primiparous Wistar rats were treated during pregnancy and lactation with doses of THC equivalent to the current estimates of moderate cannabis consumption in humans (2.5-5 mg kg(-1), per os, from gestational day 15 to postnatal day 9). The emotional reactivity of infant, adolescent, and adult offspring was investigated using the isolation-induced ultrasonic vocalization, social interaction, and elevated plus-maze tests, respectively.


RESULTS
Perinatal THC treatment did not affect parameters of reproduction; however, at the dose of 5 mg kg(-1), it increased the number of ultrasounds emitted by rat pups removed from the nest, inhibited social interaction and play behavior in the adolescent offspring, and induced an anxiogenic-like profile in the adult offspring tested in the elevated plus-maze test.


CONCLUSIONS
These results suggest that the endocannabinoid system is involved in the control of emotionality since early developmental stages. Thus, even moderate doses of cannabinoid compounds, when administered during the perinatal period, can have profound consequences for brain maturation, leading to long-lasting neurodevelopmental alterations.
Trezza
Viviana
V
Department of Physiology and Pharmacology, Sapienza University of Rome, P. le A. Moro 5, 00185 Rome, Italy.
Campolongo
Patrizia
P
Cassano
Tommaso
T
Macheda
Teresa
T
Dipasquale
Pasqua
P
Carratù
Maria Rosaria
MR
Gaetani
Silvana
S
Cuomo
Vincenzo
V
D000375:Aging / Q000523:psychology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001007:Anxiety / Q000523:psychology; D001835:Body Weight / Q000187:drug effects; D013759:Dronabinol / Q000494:pharmacology*; D004644:Emotions / Q000187:drug effects*; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects; D012919:Social Behavior; D012934:Social Isolation; D014828:Vocalization, Animal / Q000187:drug effects
D006213:Hallucinogens; D013759:Dronabinol