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Pretreatment with Δ9-tetrahydrocannabinol (THC) increases cocaine-stimulated activity in adolescent but not adult male rats.

Diana Dow-Edwards, Sari Izenwasser

Pharmacology, Biochemistry, and Behavior January 2012 DOI: 10.1016/j.pbb.2011.09.003 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Controlled animal experiment Peer reviewed
Population Adolescent (postnatal day 34) and adult (postnatal day 66) rats
Interventions Δ9-tetrahydrocannabinol (THC) cocaine
Dose 3 mg/kg/day THC for 8 days; escalating doses of cocaine
Duration 8 days of THC administration; cocaine challenge on day 12 (4 days after last THC dose)
Measures locomotor activity
Topics Cannabis
Key findings Repeated THC (3 mg/kg/day for 8 days) reduced locomotor activity in adult rats but not adolescents. After a cocaine challenge four days post-THC, adolescent rats exposed to THC showed increased locomotor responses to cocaine compared with vehicle-injected controls, an effect not seen in adults. The authors propose this age-specific sensitization may account for the greater transition to cocaine after early versus later marijuana use.

Abstract

Marijuana (Cannabis sativa) remains one of the most widely used illegal drugs, with adolescents being particularly vulnerable to its use and abuse. In spite of this, most studies are conducted in adult animals even though the effects might be quite different in adolescents. Additionally, the use of marijuana often precedes the use of other psychoactive drugs including cocaine, especially when marijuana exposure begins during early adolescence. The purpose of this study was to examine the effects of repeated Δ9-tetrahydrocannabinol (THC), the major active ingredient in marijuana, in adolescents compared to adults and to determine its subsequent effects on cocaine-stimulated activity. To this end, adolescent (postnatal day PND 34) and adult (PND 66) rats were administered 3 mg/kg/day THC for 8 days and locomotor activity was measured on days 1, 2, 7 and 8 after dosing. On day 12 (4 days after the last dose of THC), rats were injected with escalating doses of cocaine and behavior was recorded. Results show that THC depressed locomotor activity in adult rats but not in adolescents. However, following a cocaine challenge, adolescents exposed to THC showed increased locomotor responses to cocaine compared to chronic vehicle-injected controls. This was not seen in adults. These results show that the effects of cocaine are enhanced after THC in adolescents, but not adults, and that this might account for the greater transition to cocaine after early, as opposed to later, marijuana use.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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