Browsing by Author "Long, LE"

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    Adolescent rats find repeated Δ9-THC less aversive than adult rats but display greater residual cognitive deficits and changes in hippocampal protein expression following exposure
    (Springer Nature, 2007-06-20) Quinn, HR; Matsumoto, I; Callaghan, PD; Long, LE; Arnold, JC; Gunasekaran, N; Thompson, MR; Dawson, B; Mallet, PE; Kashem, MA; Matsda-Matsumoto, H; Iwazki, T; McGregor, IS
    The current study examined whether adolescent rats are more vulnerable than adult rats to the lasting adverse effects of cannabinoid exposure on brain and behavior. Male Wistar rats were repeatedly exposed to Δ9-tetrahydrocannabinol (Δ(9)-THC, 5 mg/kg i.p.) in a place-conditioning paradigm during either the adolescent (post-natal day 28+) or adult (post-natal day 60+) developmental stages. Adult rats avoided a Δ(9)-THC-paired environment after either four or eight pairings and this avoidance persisted for at least 16 days following the final Δ(9)-THC injection. In contrast, adolescent rats showed no significant place aversion. Adult Δ(9)-THC-treated rats produced more vocalizations than adolescent rats when handled during the intoxicated state, also suggesting greater drug-induced aversion. After a 10-15 day washout, both adult and adolescent Δ(9)-THC pretreated rats showed decreased social interaction, while onlyΔ (9)-THC pretreated adolescent rats showed significantly impaired object recognition memory. Seventeen days following their last Δ(9)-THC injection, rats were euthanised and hippocampal tissue processed using two-dimensional gel electrophoresis proteomics. There was no evidence of residual Δ(9)-THC being present in blood at this time. Proteomic analysis uncovered 27 proteins, many involved in regulating oxidative stress/mitochondrial functioning and cytoarchitecture, which were differentially expressed in adolescent Δ(9)-THC pretreated rats relative to adolescent controls. In adults, only 10 hippocampal proteins were differentially expressed in Δ(9)-THC compared to vehicle-pretreated controls. Overall these findings suggest that adolescent rats find repeated Δ(9)-THC exposure less aversive than adults, but that cannabinoid exposure causes greater lasting memory deficits and hippocampal alterations in adolescent than adult rats. © 2018 Springer Nature
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    Paranoid schizophrenia is characterized by increased cannabinoid CB1 receptor binding in the dorsolateral prefrontal cortex.
    (Nature Publishing Group, 2011-07-01) Dalton, VS; Long, LE; Weickert, CS; Zavitsanou, K
    A number of studies suggest a dysregulation of the endogenous cannabinoid system in schizophrenia (SCZ). In the present study, we examined cannabinoid CB1 receptor (CB1R) binding and mRNA expression in the dorsolateral prefrontal cortex (DLPFC) (Brodmann's area 46) of SCZ patients and controls, post-mortem. Receptor density was investigated using autoradiography with the CB1R ligand [3H] CP 55 940 and CB1R mRNA expression was measured using quantitative RT-PCR in a cohort of 16 patients with paranoid SCZ, 21 patients with non-paranoid SCZ and 37 controls matched for age, post-mortem interval and pH. All cases were obtained from the University of Sydney Tissue Resource Centre. Results were analyzed using one-way analysis of variance (ANOVA) and post hoc Bonferroni tests and with analysis of covariance (ANCOVA) to control for demographic factors that would potentially influence CB1R expression. There was a main effect of diagnosis on [3H] CP 55 940 binding quantified across all layers of the DLPFC (F(2,71)=3.740, p=0.029). Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB1R binding compared with the control group. When ANCOVA was employed, this effect was strengthened (F(2,67)=6.048, p=0.004) with paranoid SCZ patients differing significantly from the control (p=0.004) and from the non-paranoid group (p=0.016). In contrast, no significant differences were observed in mRNA expression between the different disease subtypes and the control group. Our findings confirm the existence of a CB1R dysregulation in SCZ and underline the need for further investigation of the role of this receptor particularly in those diagnosed with paranoid SCZ. © 2011, Nature Publishing Group.