Chronic nicotine alters cannabinoid‐mediated locomotor activity and receptor density in periadolescent but not adult male rats

Abstract

A significant number of youths use cigarettes, and more than half of the youths who smoke daily also use illicit drugs. The focus of these studies is on how exposure to nicotine affects subsequent responses to both nicotine and cannabinoids in adolescents compared with adults. We have shown previously that chronic treatment with nicotine produces sensitization to its locomotor-activating effects in female and adult rats but not male adolescent rats. To better understand the effects of nicotine on adolescent and adult rats, rats were injected with nicotine or saline for 7 days and, on day 8, either challenged with delta-9-tetrahydrocannabinol (Δ9-THC) or the cannabinoid agonist CP 55,940 and tested for locomotor activity, or the brains were removed for quantitative autoradiography studies of the cannabinoid 1 receptor. A separate group of rats was treated with nicotine plus the cannabinoid antagonist AM 251 and then challenged with CP 55,940. In adolescent male rats, nicotine administration led to sensitization to the locomotor-decreasing effects of both Δ9-THC and CP 55,940, but in adult male rats, the response to either drug was unchanged compared to controls. The effect of nicotine on CP 55,940-mediated locomotor activity was blocked by co-administration of AM 251 with the nicotine. Further, cannabinoid receptor density was increased in the prelimbic prefrontal cortex, ventral tegmental area, and select regions of the hippocampus in adolescent male rats pretreated with nicotine compared to vehicle-treated controls. There were no significant changes in cannabinoid receptor binding, however, in any of the brain regions examined in adult males pretreated with nicotine. The prelimbic prefrontal cortex and the hippocampus have been shown previously to be involved in stimulant reinforcement; thus it is possible that these changes contribute to the unique behavioral effects of chronic nicotine and subsequent drug administration in adolescents compared with adults. Keywordsautoradiography; cannabinoid; locomotor activity; nicotine; adolescent Adolescents who smoke are 11 times more likely to try marijuana than those that do not smoke, and although adolescents who already are cigarette smokers make up only 12% of marijuana non-users, they make up almost half of those who initiate marijuana use (reviewed by Hornik, *Correspondence to: Sari Izenwasser, Ph.D., E-mail: sizenwasser@med.miami.edu, Tel: +1-305-243-2032, Fax: +1-305-243-5475. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 2003). In addition, nicotine use between ages 14 and 17 yrs predicted progression to cann...

Sexually-dimorphic alterations in cannabinoid receptor density depend upon prenatal/early postnatal history

“…Brains were sectioned coronally at 20 µm, sections taken on plus slides and stored at −80°C. Sections were then processed for CB1 receptor densities using 3 H CP 55,940 binding as described in Werling et al, (2009). Frozen sections were thawed to room temperature and incubated for 2 hours with 3nM [ 3 H]CP55,940 in buffer (50mM Tris-HCl, pH 7.4 with 5%BSA).…”

Sex-specific alterations in hippocampal cannabinoid 1 receptor expression following adolescent delta-9-tetrahydrocannabinol treatment in the rat

“…Frozen sections were thawed and incubated for 2h with 3nM [ 3 H]CP55,940 in binding buffer (50mM Tris-HCl, pH 7.4, with 5% BSA), as described previously [29, 30]. Sections were washed 4× 30min in ice-cold buffer (50mM Tris-HCl with 1% BSA), followed by 5 min at 25°C in buffer containing 50mM Tris-HCl with 0.5% formaldehyde solution.…”

Prior Exposure to THC Increases the Addictive Effects of Nicotine in Rats

“…immediately before being placed into the chamber for 60 min on each of 10 days (Monday through Friday). This dose of nicotine has been previously shown to induce locomotor sensitization when given repeatedly (Werling et al, 2009). …”