Repeated exposure to Δ9-tetrahydrocannabinol alters heroin-induced locomotor sensitisation and Fos-immunoreactivity

ME Singh, IS McGregor, PE Mallet - Neuropharmacology, 2005 - Elsevier
Neuropharmacology, 2005Elsevier
The present study examined the effect of chronic exposure to Δ9-tetrahydrocannabinol
(THC) on heroin-induced locomotor sensitisation and Fos-immunoreactivity (Fos-IR). Adult
male albino Wistar rats (n= 60) were injected intraperitoneally (ip) 21 times with vehicle,
0.05, 0.5, or 5.0 mg/kg THC (once every 48h for 41 days). Locomotor activity was assessed
for 180min on pre-exposure days 1, 21, and 41. Following a 2-week washout period, rats
were divided into five equal groups (n= 12) and injected subcutaneously (sc) with vehicle or …
The present study examined the effect of chronic exposure to Δ9-tetrahydrocannabinol (THC) on heroin-induced locomotor sensitisation and Fos-immunoreactivity (Fos-IR). Adult male albino Wistar rats (n=60) were injected intraperitoneally (i.p.) 21 times with vehicle, 0.05, 0.5, or 5.0mg/kg THC (once every 48h for 41 days). Locomotor activity was assessed for 180min on pre-exposure days 1, 21, and 41. Following a 2-week washout period, rats were divided into five equal groups (n=12) and injected subcutaneously (s.c.) with vehicle or heroin (0.5mg/kg). Locomotor activity was recorded for 240min. In drug-naïve rats, heroin significantly increased locomotor activity. THC pre-exposure further increased heroin-induced locomotion. After an interval of 2 weeks, rats pre-exposed to vehicle and 5.0mg/kg THC in the first part of the experiment were randomly assigned to one of four treatment groups (n=6) and injected s.c. with vehicle or 0.5mg/kg heroin and perfused 2h later. Fos-IR was examined in several brain regions. Acute heroin increased Fos-IR in drug-naïve rats in the caudate-putamen (CPu; central, medial and dorsomedial regions), nucleus accumbens (NAC; core and shell regions), bed nucleus of the stria terminalis (BNST), lateral septum, central nucleus of the amygdala (CEA), periaqueductal grey (PAG; dorsolateral, dorsomedial, and lateral), and the Edinger–Westphal nucleus. Pre-exposure to THC significantly increased heroin-induced Fos-IR in the dorsomedial CPu and the NAC (core). Conversely, THC pre-exposure reduced heroin-induced Fos-IR in the BNST, CEA, and the PAG (dorsolateral and lateral). The present study demonstrates that THC pre-exposure increases the locomotor stimulating effects of heroin and provides new evidence for the neural correlates that may underlie cannabinoid and opioid cross-sensitisation.
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