A Model of Δ9-Tetrahydrocannabinol Self-administration and Reinstatement That Alters Synaptic Plasticity in Nucleus Accumbens

Spencer, Sade; Neuhofer, Daniela; Chioma, Vivian C.; García‐Keller, Constanza; Schwartz, Danielle; Allen, Nicholas P.; Scofield, Michael D.; Ortiz-Ithier, Tara; Kalivas, Peter W.

doi:10.1016/j.biopsych.2018.04.016

Cited by 74 publications

(86 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nosepoke discrimination was calculated based on a formula used in [12]: nosepoke discrimination index = (active nosepokesinactive nosepokes)/(active nosepokes + inactive nosepokes), where 0 indicated no discrimination between active and inactive operanda, 1 indicated complete preference for the active operandum, and -1 indicated complete preference for inactive operandum [12]. Effects of AM251 were analyzed using separate repeated-measures one-way ANOVAs.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, CBD facilitates intravenous THC self-administration in rodents [12] (but see [43]) and offsets some of the pharmacological and behavioral effects of THC in humans [44] and rodents [9]. Furthermore, a passive THC+CBD vapor preexposure regimen facilitates the acquisition of intravenous THC+CBD self-administration, possibly by offsetting the novelty of THC intoxication or aversive stimulus properties prior to operant training [12].…”

Section: Discussionmentioning

confidence: 99%

“…interaction: F(12,192)=1.95, p=.03, η p 2 =.10; post-hoc p's≤.03). Removal of cannabis increased inactive responding in all groups (F(1,32)=12.23, p=.001, η p 2 =.19).…”

mentioning

confidence: 90%

“…In line with this, pure THC selfadministration has been difficult to demonstrate at the preclinical level [11]. Rats acquire stable rates of intravenous THC:CBD (10:1) self-administration only after extended passive pre-exposure to vaporized THC:CBD [12]. Thus, studying the effects of THC in the presence of other phytocannabinoids is important for modeling cannabis use.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

Freels

Baxter-Potter

Lugo

et al. 2019

Preprint

View full text Add to dashboard Cite

Recent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug employed and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized ∆9-tetrahydrocannabinol-rich (CANTHC) or cannabidiol-rich (CANCBD) complete cannabis extracts. Male Sprague Dawley rats were trained to nosepoke for discrete puffs of CANTHC, CANCBD, or vehicle (VEH) in daily one-hour sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CANTHC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared to CANCBD or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CANTHC administration decreased hippocampal CB1 receptor binding. Removal of CANTHC reinforcement (but not CANCBD) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors. Cannabis vapor self-administration

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…interaction: F(12,192)=1.95, p=.03, η p 2 =.10; post-hoc p's≤.03). Removal of cannabis increased inactive responding in all groups (F(1,32)=12.23, p=.001, η p 2 =.19).…”

mentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

Freels

Baxter-Potter

Lugo

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Recent data have demonstrated that cannabinoids, experimenter-or self-administered, abolish LTD in the NAc (Mato et al, 2004(Mato et al, , 2005Neuhofer and Kalivas, 2018;Spencer et al, 2018). Thus, we sought to determine if perinatal WIN exposure elicited similar deficits in LTD in the NAc at adulthood.…”

Section: Perinatal Exposure To Win Alters Synaptic Plasticity and Celmentioning

confidence: 97%

Maternal exposure to the cannabinoid agonist WIN 55,12,2 during lactation induces lasting behavioral and synaptic alterations in the rat adult offspring of both sexes

Scheyer

Borsoi

Pélissier-Alicot

et al. 2020

Preprint

View full text Add to dashboard Cite

Consumption of cannabis during pregnancy and the lactation period is a rising public health concern (Scheyer et al., 2019). We have previously shown that exposure to synthetic or plant-derived cannabinoids via lactation disrupts perinatal programming of the gamma-aminobutyric acid trajectory in the prefrontal cortex and early-life behaviors (Scheyer et al., 2020b). Recently, we described lasting behavioral and neuronal consequences of ∆ 9-tetrahydrocannabinol (THC) perinatal exposure via lactation (Scheyer et al., 2020a).Here, we extend upon these findings by testing the effects in offspring of maternal exposure to the synthetic cannabinoid agonist WIN 55,12,2 (WIN). The data demonstrate that rats exposed during lactation to WIN display social, cognitive and motivational deficits at adulthood. These behavioral changes were paralleled by a specific loss of endocannabinoid-mediated long-term depression in the prefrontal cortex and nucleus accumbens, while other forms of synaptic plasticity remained intact. Thus, similarly to THC, perinatal WIN exposure via lactation induces behavioral and synaptic abnormalities lasting into adulthood.

show abstract

Effects in rats of adolescent exposure to cannabis smoke or THC on emotional behavior and cognitive function in adulthood

et al. 2019

View full text Add to dashboard Cite

A Model of Δ9-Tetrahydrocannabinol Self-administration and Reinstatement That Alters Synaptic Plasticity in Nucleus Accumbens

Abstract: We report enduring consequences of THC+CBD use on critical relapse circuitry and synaptic physiology in NAcore following rat self-administration and provide the first report of cue- and stress-induced reinstatement with this model.

Cited by 74 publications

References 68 publications

Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

Maternal exposure to the cannabinoid agonist WIN 55,12,2 during lactation induces lasting behavioral and synaptic alterations in the rat adult offspring of both sexes

Effects in rats of adolescent exposure to cannabis smoke or THC on emotional behavior and cognitive function in adulthood

Contact Info

Product

Resources

About