Transgenerational effects of exogenous cannabinoid exposure

A paper in the October issue of the Journal of Psychopharmacology will be of interest to my readership. It looks at the consequences of exposure to an exogenous cannabinoid agonist

Byrnes JJ, Johnson NL, Schenk ME, Byrnes EM. Cannabinoid exposure in adolescent female rats induces transgenerational effects on morphine conditioned place preference in male offspring.J Psychopharmacol October 2012 26: 1348-1354, first published on April 19, 2012 doi:10.1177/0269881112443745 [ PubMed ]

In this study the authors exposed 23 day old (adolescent) female Sprague-Dawley rats to a three day, twice per day regimen of WIN 55,212-2 which is a full agonist at the CB1 receptor. The more familiar exogenous cannabinoid, Δ⁹-tetrahydrocannabinol (THC) is a partial agonist at the same site. The authors waited until the animals were adult (60 days), bred them and then examined the subsequent male off-spring of these mothers. They assay of interest was the Conditioned Place Preference test which is one common method to assess subjective drug liking in rats and mice.

The idea is to take a chamber which is divided into two or there sections by dividers and doors (in this case it was a three-chamber apparatus). The chambers are differentiated by salient stimuli such as the floor texture or type, wall stripes (horizontal vs vertical), etc. You let the subject explore at will in pre-conditioning baseline studies. Then, you conduct a series of conditioning sessions in which the animal is injected with a drug and then confined in one of the chambers. On other sessions the animal is injected with the drug vehicle only and confined to the other chamber. In this case, there were three active drug and saline conditioning sessions. Finally, on a later test day the animal is allowed once again to freely explore all of the chambers. The amount of time it spends in each chamber is recorded and the relative preference for the drug-paired chamber over the saline-paired chamber can be expressed, typically as a difference in amount of time, or the percentage of the total time, spent exploring the drug-paired chamber.

The figure presents Conditioned Place Preference data for the adult male offspring (WIN-F1) of mothers which were exposed to WIN 55,212-2 in adolescence and in the control group (VEH-F1) of adult male offspring of mothers treated twice a day for three days with the drug vehicle. There were three different place conditioning levels with groups of animals from the VEH and WIN treated dams place conditioned (in adulthood) with saline, 1 or 5 mg/kg of morphine. As expected, the chamber preferences of animals “conditioned” with vehicle were indistinguishable, i.e., they spent approximately equal time in each chamber. Animals conditioned with morphine, however, spent more time in the drug-paired chamber than in the vehicle-paired chamber.

Interestingly, there was a group difference which depended on the maternal treatment. The offspring of the WIN treated mothers appeared more sensitive to the rewarding effects of morphine because they expressed a conditioned place preference after 1 mg/kg training, unlike the adult offspring of VEH exposed dams. Although I’m not showing it here, the study also looked at adolescent male offspring and found a similar enhancement of morphine place-preference conditioning in the offspring of WIN exposed dams.

The translational take-away is pretty clear and fairly frightening. It suggests that one of the reasons for familial patterns of substance abuse may not simply be down to genetic legacy but may have something to do with drug exposures of the mother.