Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during
adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC)
exposure during postnatal days 35–49 was made in maternal deprived (D) or non-deprived (animal facility rearing, AFR) rats. The effects
of dronabinol exposure were studied after 2 weeks of washout on the rewarding effects of morphine measured in the place preference
and oral self-administration tests. The preproenkephalin (PPE) mRNA levels and the relative density and functionality of CB1, and
m-opioid receptors were quantified in the striatum and the mesencephalon. Chronic dronabinol exposure in AFR rats induced an
increase in sensitivity to morphine conditioning in the place preference paradigm together with a decrease of PPE mRNA levels in the
nucleus accumbens and the caudate–putamen nucleus, without any modification for preference to oral morphine consumption. In
contrast, dronabinol treatment on D-rats normalized PPE decrease in the striatum, morphine consumption, and suppressed sensitivity to
morphine conditioning. CB1 and m-opioid receptor density and functionality were not changed in the striatum and mesencephalon of all
groups of rats. These results indicate THC potency to act as a homeostatic modifier that would worsen the reward effects of morphine
on naive animals, but ameliorate the deficits in maternally D-rats. These findings point to the self-medication use of cannabis in subgroups
of individuals subjected to adverse postnatal environment.