Cannabinoid-induced Behavioral Sensitization in Adolescent Sprague-Dawley Rats

Adolescent cannabis use has grown because of increased availability and higher societal acceptance. This increase in cannabis use is problematic as adolescents who experiment with cannabis are more likely to abuse cannabis and experiment with other illicit drugs such as cocaine. The reason for the greater susceptibility to drugs use is unclear and may be the result of altered drug sensitivity after cannabis exposure. Thus, the present investigation used the behavioral sensitization paradigm to examine the behavioral response of early adolescent rats to the cannabinoid agonist CP 55,940 (CP) or cocaine after repeated cannabinoid administration. It was hypothesized that: (1) CP would cause a sensitized response in both male and female adolescent rats, (2) female rats would have a greater behavioral response than male rats, (3) pretreatment with CP would induce cross-sensitization to cocaine, (4) pretreatment with cocaine would cause behavioral sensitization and conditioned activity in male and female adolescent rats. In the first experiment, 137 male and female Sprague-Dawley rats were given CP (4, 13.2, or 40 µg/kg, IP) or vehicle (50% DMSO/H2O) once daily for 5 consecutive days on postnatal day (PD) 30- PD 34. Distance traveled and stereotyped movement was assessed for 1 h after each drug injection. After a 48 h abstinence period (i.e., on PD 36), rats were given CP (4 or 13.2 µg/kg, IP) and distance traveled and stereotyped movement was monitored for 2 h. In the second experiment, 146 male and female rats were tested with the same protocol as in Experiment 1 except that rats were given CP (13.2 or 4 µg/kg), cocaine (20 mg/kg), or vehicle (saline or 50% DMSO/H2O) for five days and then tested with saline or cocaine (10 mg/kg) after 48 h. In the first experiment, no dose of CP altered distance traveled scores or stereotyped movement over the five pre-exposure days nor did CP cause behavioral sensitization on the test day. In the second experiment, pretreatment with cocaine led to enhanced distance traveled scores and stereotyped movement when challenged with cocaine (behavioral sensitization) or saline (conditioned activity) on test day. In contrast, CP-pretreated rats did not show greater activity when injected with cocaine or saline on test day. These data show that cannabinoids do not act like psychostimulant drugs, since CP did not cause the same changes in drug sensitivity as cocaine. The cocaine sensitization observed in adolescent rats indicates that this age group is particularly vulnerable to the rewarding effects of cocaine, and suggests that early cocaine exposure can augment drug seeking behavior. The failure to detect cannabinoid-induced sensitization, conditioned activity, or cocaine cross-sensitization during adolescence suggests that CP, when given at a consistent dose, does not increase the addictive properties of cannabinoids or cocaine. The results also indicate that cannabinoid use does not alter drug responsivity or lead to greater drug seeking and abuse in the adolescent population