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In the present study, the effects of perinatal exposure to Delta(9)-tetrahydrocannabinol (THC) on heroin-induced place conditioning and Fos-immunoreactivity (Fos-IR) were examined. Male albino Wistar rats (N=104) were pretreated with vehicle (n=52) or 5 mg/kg THC (n=52) from postnatal days 4 through 14. At approximately 8 weeks of age, 72 rats were divided into six equal groups (n=12 per group) and injected subcutaneously (s.c.) with vehicle, 0.5, or 2.0 mg/kg heroin and tested in an unbiased two-compartment place conditioning task. In vehicle-pretreated rats, 2.0 mg/kg but not 0.5 mg/kg heroin produced a significant place preference. Perinatal THC exposure significantly enhanced the rewarding properties of both doses of heroin. In the second experiment, 32 rats were divided into four equal groups (n=8 per group) and injected with vehicle or 0.5 mg/kg heroin s.c. and perfused 2-h later. Fos-IR was examined in several brain regions directly or indirectly involved in reward. Acute administration of heroin in vehicle pretreated rats increased Fos-IR in the central, medial, and dorsomedial caudate putamen (CPu), nucleus accumbens (NAC, core and shell regions), lateral septum, islands of Calleja-major (ICjM), bed nucleus of the stria terminalis (BNST), central nucleus of the amygdala (CEA), dorsolateral and dorsomedial periaqueductal gray (PAG), ventral tegmental area (VTA), Edinger-Westphal nucleus (EW). Perinatal THC exposure significantly increased heroin-induced Fos-IR in the dorsomedial CPu. Conversely, perinatal THC exposure reduced heroin-induced Fos-IR in the NAC (shell), BNST, CEA, dorsolateral and lateral PAG, VTA, and EW. The present study demonstrates an increase in the rewarding properties of heroin following exposure to THC at an early age and provides new evidence regarding possible neural correlates underlying this behavioral alteration. Neuropsychopharmacology (2006) 31, 58-69. doi:10.1038/sj.npp.1300770; published online 25 May 2005.

Perinatal Exposure to Δ9-Tetrahydrocannabinol Alters Heroin-Induced Place Conditioning and Fos-Immunoreactivity