{"id":{"repo_id":"vcu","oai_identifier":"oai:scholarscompass.vcu.edu:etd-1554"},"canonical_url":"https://search.dev.ndltd.org/etd/vcu/oai:scholarscompass.vcu.edu:etd-1554","repository":{"repo_id":"vcu","name":"Virginia Commonwealth University","base_url":"https://scholarscompass.vcu.edu/do/oai/"},"display":{"title":"Cannabinoid Modulation of Reinforcement Maintained by Stimulation of the Medial Forebrain Bundle in C57Bl/6J Mice","abstract":"Cannabinoid agonists, including marijuana containing delta-9-tetrahydrocannabinol (THC), are found rewarding by humans. In addition to human self-reports and experimental studies that show marijuana is rewarding, contributions from preclinical studies also have implicated cannabinoid receptors in reward-motivated behavior. One way to assess these preclinical effects of cannabinoids is intracranial self-stimulation (ICSS), where an animal performs a response to receive electrical stimulation of a specific brain area or circuit known to be involved in reward. Drugs of abuse, such as psychomotor stimulants, facilitate responding for ICSS. While a few studies have shown facilitating effects of cannabinoids in rats, several have shown the opposite effect, and no studies so far have evaluated cannabinoids in mouse ICSS. Furthermore there are no studies evaluating specific inhibitors of endocannabinoid catabolic enzymes in ICSS in any species. In these studies we assessed the cannabinoid agonist THC, as well as the fatty acid amide hydrolase (FAAH) inhibitor, PF-3845, the monoacylglycerol lipase (MAGL) inhibitor JZL184, and the combined FAAH/MAGL inhibitor SA-57 in ICSS of the medial forebrain bundle in C57BL/6 mice. Additionally, we assessed the psychomotor stimulant cocaine as a positive control to facilitate ICSS. These studies were complimented with spontaneous locomotor activity and food-maintained operant experiments to assess the sensitivity of ICSS to cannabinoids. Additionally, brain endocannabinoid levels were measured in brain regions associated with the mesolimbic system after enzyme inhibitor treatments. THC, JZL184, and SA-57 all produced time-dependent reductions in ICSS that were mediated through CB1 receptors, as they were blocked by pre-treatment with the CB1 antagonist rimonabant, but not with the CB2 antagonist SR144528. PF-3845 also reduced ICSS, but did so independent of CB1 and CB2 receptors, and only with one dose (30.0 mg/kg) that has not been assessed previously in vivo. We showed that ICSS was more sensitive to the rate-reducing effects of cannabinoids than other measures of behavior with motor components including spontaneous locomotor activity and operant nose-poking for food, and that the reduction of ICSS produced by both JZL184 and SA-57 is accompanied by increases in 2-AG in mesolimbic brain areas. Thus, cannabinoids do not facilitate ICSS in C57BL/6 mice over a range of doses and pre-treatment times, similar to most studies with rats. These data suggest that cannabinoids may produce rewarding effects through non-mesolimbic areas of the brain.","abstract_html":"Cannabinoid agonists, including marijuana containing delta-9-tetrahydrocannabinol (THC), are found rewarding by humans. In addition to human self-reports and experimental studies that show marijuana is rewarding, contributions from preclinical studies also have implicated cannabinoid receptors in reward-motivated behavior. One way to assess these preclinical effects of cannabinoids is intracranial self-stimulation (ICSS), where an animal performs a response to receive electrical stimulation of a specific brain area or circuit known to be involved in reward. Drugs of abuse, such as psychomotor stimulants, facilitate responding for ICSS. While a few studies have shown facilitating effects of cannabinoids in rats, several have shown the opposite effect, and no studies so far have evaluated cannabinoids in mouse ICSS. Furthermore there are no studies evaluating specific inhibitors of endocannabinoid catabolic enzymes in ICSS in any species. In these studies we assessed the cannabinoid agonist THC, as well as the fatty acid amide hydrolase (FAAH) inhibitor, PF-3845, the monoacylglycerol lipase (MAGL) inhibitor JZL184, and the combined FAAH/MAGL inhibitor SA-57 in ICSS of the medial forebrain bundle in C57BL/6 mice. Additionally, we assessed the psychomotor stimulant cocaine as a positive control to facilitate ICSS. These studies were complimented with spontaneous locomotor activity and food-maintained operant experiments to assess the sensitivity of ICSS to cannabinoids. Additionally, brain endocannabinoid levels were measured in brain regions associated with the mesolimbic system after enzyme inhibitor treatments. THC, JZL184, and SA-57 all produced time-dependent reductions in ICSS that were mediated through CB1 receptors, as they were blocked by pre-treatment with the CB1 antagonist rimonabant, but not with the CB2 antagonist SR144528. PF-3845 also reduced ICSS, but did so independent of CB1 and CB2 receptors, and only with one dose (30.0 mg/kg) that has not been assessed previously in vivo. We showed that ICSS was more sensitive to the rate-reducing effects of cannabinoids than other measures of behavior with motor components including spontaneous locomotor activity and operant nose-poking for food, and that the reduction of ICSS produced by both JZL184 and SA-57 is accompanied by increases in 2-AG in mesolimbic brain areas. Thus, cannabinoids do not facilitate ICSS in C57BL/6 mice over a range of doses and pre-treatment times, similar to most studies with rats. These data suggest that cannabinoids may produce rewarding effects through non-mesolimbic areas of the brain.","abstract_has_math":false,"creators":["Wiebelhaus, Jason"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":"Psychology","degree_department":null,"school":null,"contributors":["Aron Lichtman","Joseph Porter"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-09-20T07:00:00Z","date_published":"2013-09-20T07:00:00Z","updated_at":"2026-07-24T05:54:02Z","subjects":["cannabinoid","THC","ICSS","endocannabinoid","anandamide","2-AG","AEA","locomotor activity","operant responding","Psychology","Social and Behavioral Sciences"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/555"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/555","href":"https://scholarscompass.vcu.edu/etd/555","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/930T-TT05","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Aron Lichtman","Joseph Porter"]},{"key":"dc:creator","label":"Author","values":["Wiebelhaus, Jason"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2018-10-24T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Psychology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["cannabinoid","THC","ICSS","endocannabinoid","anandamide","2-AG","AEA","locomotor activity","operant responding","Psychology","Social and Behavioral Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["© The Author"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.25772/930T-TT05","https://scholarscompass.vcu.edu/etd/555"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Cannabinoid agonists, including marijuana containing delta-9-tetrahydrocannabinol (THC), are found rewarding by humans. In addition to human self-reports and experimental studies that show marijuana is rewarding, contributions from preclinical studies also have implicated cannabinoid receptors in reward-motivated behavior. One way to assess these preclinical effects of cannabinoids is intracranial self-stimulation (ICSS), where an animal performs a response to receive electrical stimulation of a specific brain area or circuit known to be involved in reward. Drugs of abuse, such as psychomotor stimulants, facilitate responding for ICSS. While a few studies have shown facilitating effects of cannabinoids in rats, several have shown the opposite effect, and no studies so far have evaluated cannabinoids in mouse ICSS. Furthermore there are no studies evaluating specific inhibitors of endocannabinoid catabolic enzymes in ICSS in any species. In these studies we assessed the cannabinoid agonist THC, as well as the fatty acid amide hydrolase (FAAH) inhibitor, PF-3845, the monoacylglycerol lipase (MAGL) inhibitor JZL184, and the combined FAAH/MAGL inhibitor SA-57 in ICSS of the medial forebrain bundle in C57BL/6 mice. Additionally, we assessed the psychomotor stimulant cocaine as a positive control to facilitate ICSS. These studies were complimented with spontaneous locomotor activity and food-maintained operant experiments to assess the sensitivity of ICSS to cannabinoids. Additionally, brain endocannabinoid levels were measured in brain regions associated with the mesolimbic system after enzyme inhibitor treatments. THC, JZL184, and SA-57 all produced time-dependent reductions in ICSS that were mediated through CB1 receptors, as they were blocked by pre-treatment with the CB1 antagonist rimonabant, but not with the CB2 antagonist SR144528. PF-3845 also reduced ICSS, but did so independent of CB1 and CB2 receptors, and only with one dose (30.0 mg/kg) that has not been assessed previously in vivo. We showed that ICSS was more sensitive to the rate-reducing effects of cannabinoids than other measures of behavior with motor components including spontaneous locomotor activity and operant nose-poking for food, and that the reduction of ICSS produced by both JZL184 and SA-57 is accompanied by increases in 2-AG in mesolimbic brain areas. Thus, cannabinoids do not facilitate ICSS in C57BL/6 mice over a range of doses and pre-treatment times, similar to most studies with rats. These data suggest that cannabinoids may produce rewarding effects through non-mesolimbic areas of the brain."]},{"key":"dc:title","label":"Title","values":["Cannabinoid Modulation of Reinforcement Maintained by Stimulation of the Medial Forebrain Bundle in C57Bl/6J Mice"]}]}],"canonical_facts":{"dc:contributor":["Aron Lichtman","Joseph Porter"],"dc:creator":["Wiebelhaus, Jason"],"dc:date.available":["2018-10-24T07:00:00Z"],"dc:description.abstract":["Cannabinoid agonists, including marijuana containing delta-9-tetrahydrocannabinol (THC), are found rewarding by humans. In addition to human self-reports and experimental studies that show marijuana is rewarding, contributions from preclinical studies also have implicated cannabinoid receptors in reward-motivated behavior. One way to assess these preclinical effects of cannabinoids is intracranial self-stimulation (ICSS), where an animal performs a response to receive electrical stimulation of a specific brain area or circuit known to be involved in reward. Drugs of abuse, such as psychomotor stimulants, facilitate responding for ICSS. While a few studies have shown facilitating effects of cannabinoids in rats, several have shown the opposite effect, and no studies so far have evaluated cannabinoids in mouse ICSS. Furthermore there are no studies evaluating specific inhibitors of endocannabinoid catabolic enzymes in ICSS in any species. In these studies we assessed the cannabinoid agonist THC, as well as the fatty acid amide hydrolase (FAAH) inhibitor, PF-3845, the monoacylglycerol lipase (MAGL) inhibitor JZL184, and the combined FAAH/MAGL inhibitor SA-57 in ICSS of the medial forebrain bundle in C57BL/6 mice. Additionally, we assessed the psychomotor stimulant cocaine as a positive control to facilitate ICSS. These studies were complimented with spontaneous locomotor activity and food-maintained operant experiments to assess the sensitivity of ICSS to cannabinoids. Additionally, brain endocannabinoid levels were measured in brain regions associated with the mesolimbic system after enzyme inhibitor treatments. THC, JZL184, and SA-57 all produced time-dependent reductions in ICSS that were mediated through CB1 receptors, as they were blocked by pre-treatment with the CB1 antagonist rimonabant, but not with the CB2 antagonist SR144528. PF-3845 also reduced ICSS, but did so independent of CB1 and CB2 receptors, and only with one dose (30.0 mg/kg) that has not been assessed previously in vivo. We showed that ICSS was more sensitive to the rate-reducing effects of cannabinoids than other measures of behavior with motor components including spontaneous locomotor activity and operant nose-poking for food, and that the reduction of ICSS produced by both JZL184 and SA-57 is accompanied by increases in 2-AG in mesolimbic brain areas. Thus, cannabinoids do not facilitate ICSS in C57BL/6 mice over a range of doses and pre-treatment times, similar to most studies with rats. These data suggest that cannabinoids may produce rewarding effects through non-mesolimbic areas of the brain."],"dc:identifier":["https://doi.org/10.25772/930T-TT05","https://scholarscompass.vcu.edu/etd/555"],"dc:rights":["© The Author"],"dc:subject":["cannabinoid","THC","ICSS","endocannabinoid","anandamide","2-AG","AEA","locomotor activity","operant responding","Psychology","Social and Behavioral Sciences"],"dc:title":["Cannabinoid Modulation of Reinforcement Maintained by Stimulation of the Medial Forebrain Bundle in C57Bl/6J Mice"],"thesis:degree_discipline":["Psychology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:54:02Z"}