Chronic Cannabinoid Administration to Periadolescent Rats Modulates the Metabolic Response to Acute Cocaine in the Adult Brain

Abstract

Purpose: To analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid exposure during periadolescence. Procedures: The synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence. When these animals reached adulthood, saline and cocaine-induced changes in 2-deoxy-2-[18 F]fluoro D glucose (FDG) uptake were studied by positron emission tomography.Results: The baseline (post-saline) metabolism in the septal nuclei was higher in CP-females than in VH-females, although septal metabolism was lower in CP-females after cocaine, reaching similar values to those of VH-females at baseline. Cocaine did not affect metabolism in VH-females. Periadolescent cannabinoid treatment did not influence baseline metabolism in males although cocaine reduced the FDG uptake in the dorsal striatum of males that received the VH but not CP. Conclusions: These results suggest that cannabinoids during periadolescence modify baseline and cocaine-evoked brain metabolism in a sex-dependent manner. In the case of CP-females, the involvement of septal metabolic alterations in their susceptibility to the rewarding effects of cocaine should be further investigated.

Functional neuroimaging of amphetamine-induced striatal neurotoxicity in the pleiotrophin knockout mouse model

“…Despite existing evidence based on the results of imaging techniques in humans [31,36], few studies have used [ 18 F]-FDG-PET to explore the effects of drugs in animal models [13,35]. This gap in knowledge is significant, considering that the most remarkable advances in the characterization of the mechanisms underlying psychostimulants-induced neurotoxicity have been achieved in rodent models.…”

Effects of Cannabinoid Exposure during Neurodevelopment on Future Effects of Drugs of Abuse: A Preclinical Perspective

“…Research on CP55,940 and HU-210 generated unique data across genders where metabolic responses to amphetamine insults were analysed. CP55,940 was observed to differentially affect cocaine metabolism of females in comparison to males [ 131 , 132 ]. Females in CP55,940-treated groups were observed to self-administer a significantly greater amount of cocaine, with this sensitivity in females further replicated when rodents were exposed to HU-210 [ 46 ].…”

“…Research analysing the effects of cannabinoid exposure on subsequent cocaine activity has utilised metabolic approaches which allow for the development of more specific insights into the region-specific effect of cocaine. For instance, researchers have analysed the brains metabolic responses to cocaine in both male and female Wistar rats exposed to CP55,940 during adolescence which resulted in a region specific understanding of drug metabolism [ 132 ]. To achieve this, Wistar males and females were mated with subsequent litters gender balanced and utilised for experimentation.…”

Testing the Role of Δ9-Tetrahydrocannabinol During Adolescence as a Gateway Drug: Behavioural, Brain Imaging and Transcriptomic Studies

“…However, two previous reports by our group suggested that adolescent exposure to the synthetic cannabinoid CP 55,940 modifies brain metabolism in the frontal and amygdalo-entorhinal cortices in females (82). Moreover, the brain responses to a cocaine injection were also different in animals exposed to CP 55,940 during adolescence (83). Although these results should be replicated, they represent the first PET evidence indicative of a long-lasting alteration in the cerebellum.…”

“…While several reports in the human literature have documented long-lasting effects of cannabis consumption on brain structure and function during adolescence (41,42), there is a paucity of this type of research using animal models. In two previous reports by our group, we used positron emission tomography -PET-imaging to study the long-term functional consequences of adolescent cannabinoid exposure on adult brain function finding alterations in the frontal and amygdalo-entorhinal cortices, the septal nuclei and the striatum (23,43). However, no structural imaging or metabolic studies have been performed up to this date.…”