In the United States, marijuana is one of the drugs most abused by adolescents, with females representing a growing number of users. In previous studies, treatment of adolescent female rats with morphine significantly altered brain reward systems in future offspring. As both cannabinoid and opioid systems develop during adolescence, it was hypothesized that early exposure to cannabinoids would induce similar transgenerational effects. In the current study, female rats were treated with the cannabinoid receptor (CB1/CB2) agonist WIN 55,212-2 or its vehicle for three consecutive days during adolescent development (30 days of age), and were subsequently mated in adulthood (60 days of age). The adolescent and adult male offspring of these WIN 55,212-2 (WIN-F1)- or vehicle (VEH-F1)-treated females were tested for their response to morphine using the conditioned place preference (CPP) paradigm. Both adolescent and adult WIN-F1offspring exhibited greater sensitivity to morphine CPP than their VEH-F1 counterparts. Collectively, the findings provide additional evidence of transgenerational effects of adolescent drug use.
ByrnesEM (2005) Transgenerational consequences of adolescent morphine exposure in female rats: Effects on anxiety-like behaviors and morphine sensitization in adult offspring. Psychopharmacology (Berl)182: 537–544.
2.
CampbellJOWoodRDSpearLP (2000) Cocaine and morphine-induced place conditioning in adolescent and adult rats. Physiol Behav68: 487–493.
3.
CampolongoPTrezzaVRatanoP. (2011) Developmental consequences of perinatal cannabis exposure: Behavioral and neuroendocrine effects in adult rodents. Psychopharmacology (Berl)214: 5–15.
4.
DayNLGoldschmidtLThomasCA (2006) Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14. Addiction101: 1313–1322.
5.
EllgrenMSpanoSMHurdYL (2007) Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology32: 607–615.
6.
EllgrenMArtmannATkalychO. (2008) Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. Eur Neuropsychopharmacol18: 826–834.
7.
FriedPA (2002) Adolescents prenatally exposed to marijuana: Examination of facets of complex behaviors and comparisons with the influence of in utero cigarettes. J Clin Pharmacol42: 97S–102S.
8.
GammonCMFreemanGMJrXieW. (2005) Regulation of gonadotropin-releasing hormone secretion by cannabinoids. Endocrinology146: 4491–4499.
9.
GibsonMJKriegerDT (1981) Circadian corticosterone rhythm and stress response in rats with adrenal autotransplants. Am J Physiol240: E363–E366.
10.
GoldschmidtLRichardsonGACorneliusMD. (2004) Prenatal marijuana and alcohol exposure and academic achievement at age 10. Neurotoxicol Teratol26: 521–532.
11.
HouchiHBabovicDPierreficheO. (2005) CB1 receptor knockout mice display reduced ethanol-induced conditioned place preference and increased striatal dopamine D2 receptors. Neuropsychopharmacology30: 339–349.
12.
KlugmannMKlippensteinVLewekeFM. (2011) Cannabinoid exposure in pubertal rats increases spontaneous ethanol consumption and NMDA receptor associated protein levels. Int J Neuropsychopharmacol14: 505–517.
13.
Lopez-MorenoJAGonzalez-CuevasGMorenoG. (2008) The pharmacology of the endocannabinoid system: Functional and structural interactions with other neurotransmitter systems and their repercussions in behavioral addiction. Addict Biol13: 160–187.
14.
Lopez-MorenoJALopez-JimenezAGorritiMA. (2010) Functional interactions between endogenous cannabinoid and opioid systems: Focus on alcohol, genetics and drug-addicted behaviors. Curr Drug Targets11: 406–428.
15.
MartinMLedentCParmentierM. (2000) Cocaine, but not morphine, induces conditioned place preference and sensitization to locomotor responses in CB1 knockout mice. Eur J Neurosci12: 4038–4046.
16.
MereuGFaMFerraroL. (2003) Prenatal exposure to a cannabinoid agonist produces memory deficits linked to dysfunction in hippocampal long-term potentiation and glutamate release. Proc Natl Acad Sci U S A100: 4915–4920.
17.
PertweeRG (1997) Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther74: 129–180.
18.
PistisMPerraSPillollaG. (2004) Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biol Psychiatry56: 86–94.
19.
PontieriFEMonnazziPScontriniA. (2001) Behavioral sensitization to heroin by cannabinoid pretreatment in the rat. Eur J Pharmacol421: R1–R3.
20.
RamosJAGomezMde MiguelR (2005) Effects on development. In: Handb Exp Pharmacology; Cannabinoids. Germany: Springer. pp. 643–656.
21.
RobinsonTEBerridgeKC (1993) The neural basis of drug craving: An incentive-sensitization theory of addiction. Brain Res Brain Res Rev18: 247–291.
22.
Rodriguez de FonsecaFRamosJABonninA. (1993) Presence of cannabinoid binding sites in the brain from early postnatal ages. Neuroreport4: 135–138.
23.
RubioPRodriguezdeFonsecaFMartin-CalderonJL. (1998) Maternal exposure to low doses of delta9-tetrahydrocannabinol facilitates morphine-induced place conditioning in adult male offspring. Pharmacol Biochem Behav61: 229–238.
24.
SAMHSA (2011) Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings. Substance Abuse and Mental Health Services Administration, 2011, Rockville, MD, USA: NSDUHSeries H-41 HHS Publication No. (SMA) 11–4658.
25.
SchneiderM (2008) Puberty as a highly vulnerable developmental period for the consequences of cannabis exposure. Addict Biol13: 253–263.
26.
SchneiderM (2009) Cannabis use in pregnancy and early life and its consequences: Animal models. Eur Arch Psychiatry Clin Neurosci259: 383–393.
27.
SchneiderMSchomigELewekeFM (2008) Acute and chronic cannabinoid treatment differentially affects recognition memory and social behavior in pubertal and adult rats. Addict Biol13: 345–357.
28.
SinghMEVertyANMcGregorIS. (2004) A cannabinoid receptor antagonist attenuates conditioned place preference but not behavioural sensitization to morphine. Brain Res1026: 244–253.
29.
SpanoMSFaddaPFrattaW. (2010) Cannabinoid-opioid interactions in drug discrimination and self-administration: Effect of maternal, postnatal, adolescent and adult exposure to the drugs. Curr Drug Targets11: 450–461.
30.
SteinerHBonnerTIZimmerAM. (1999) Altered gene expression in striatal projection neurons in CB1 cannabinoid receptor knockout mice. Proc Natl Acad Sci U S A96: 5786–5790.
31.
VelaGFuentesJABonninA. (1995) Perinatal exposure to delta 9-tetrahydrocannabinol (delta 9-THC) leads to changes in opioid-related behavioral patterns in rats. Brain Res680: 142–147.
32.
VelaGMartinSGarcia-GilL. (1998) Maternal exposure to delta9-tetrahydrocannabinol facilitates morphine self-administration behavior and changes regional binding to central mu opioid receptors in adult offspring female rats. Brain Res807: 101–109.
33.
WengerTGerendaiIFezzaF. (2002) The hypothalamic levels of the endocannabinoid, anandamide, peak immediately before the onset of puberty in female rats. Life Sci70: 1407–1414.
34.
WhiteDAMichaelsCCHoltzmanSG (2008) Periadolescent male but not female rats have higher motor activity in response to morphine than do adult rats. Pharmacol Biochem Behav89: 188–199.
