Restricted accessResearch articleFirst published online 2011-12
Adolescent exposure to nicotine and/or the cannabinoid agonist CP 55,940 induces gender-dependent long-lasting memory impairments and changes in brain nicotinic and CB 1 cannabinoid receptors
We have analysed the long-term effects of adolescent (postnatal day 28–43) exposure of male and female rats to nicotine (NIC, 1.4 mg/kg/day) and/or the cannabinoid agonist CP 55,940 (CP, 0.4 mg/kg/day) on the following parameters measured in the adulthood: (1) the memory ability evaluated in the object location task (OL) and in the novel object test (NOT); (2) the anxiety-like behaviour in the elevated plus maze; and (3) nicotinic and CB1 cannabinoid receptors in cingulated cortex and hippocampus. In the OL, all pharmacological treatments induced significant decreases in the DI of females, whereas no significant effects were found among males. In the NOT, NIC-treated females showed a significantly reduced DI, whereas the effect of the cannabinoid agonist (a decrease in the DI) was only significant in males. The anxiety-related behaviour was not changed by any drug. Both, nicotine and cannabinoid treatments induced a long-lasting increase in CB1 receptor activity (CP-stimulated GTPγS binding) in male rats, and the nicotine treatment also induced a decrease in nicotinic receptor density in the prefrontal cortex of females. The results show gender-dependent harmful effects of both drugs and long-lasting changes in CB1 and nicotinic receptors.
AdrianiWLaviolaG (2004) Windows of vulnerability to psychopathology and therapeutic strategy in the adolescent rodent model. Behav Pharmacol15: 341–352.
2.
AgrawalALynskeyMTMaddenPAPergadiaMLBucholzKKHeathAC (2009) Simultaneous cannabis and tobacco use and cannabis-related outcomes in young women. Drug Alcohol Depend101: 8–12.
3.
AmeriA (1999) The effects of cannabinoids on the brain. Prog Neurobiol58: 315–348.
4.
ArthurDLevinED (2002) Chronic inhibition of alpha4beta2 nicotinic receptors in the ventral hippocampus of rats: impacts on memory and nicotine response. Psychopharmacology (Berl)160: 140–145.
5.
BarkerGRBirdFAlexanderVWarburtonEC (2007) Recognition memory for objects, place and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex. J Neurosci27: 2948–2957.
6.
BiscaiaMMarínSFernándezB. (2003) Chronic treatment with CP 55,940 during the peri-adolescent period differentially affects the behavioural responses of male and female rats in adulthood. Psychopharmacology (Berl)170: 301–308.
7.
CastelliMPPirasAPD’AgostinoA. (2007) Dysregulation of the endogenous cannabinoid system in adult rats prenatally treated with the cannabinoid agonist Win 55,212-2. Eur J Pharmacol573: 11–19.
8.
CrewsFHeJHodgeC (2007) Adolescent cortical development: a critical period of vulnerability for addiction. Pharmacol Biochem Behav86: 189–199.
9.
DixSLAggletonJP (1999) Extending the spontaneous preference test of recognition: evidence of object-location and object-context recognition. Behav Brain Res99: 191–200.
10.
EgertonAAllisonCBrettRRPrattJA (2006) Cannabinoids and prefrontal cortical function: insights from preclinical studies. Neurosci Biobehav Rev30: 680–695.
11.
EichenbaumH (2004) Hippocampus cognitive processes and neural representations that underlie declarative memory. Neuron44: 109–120.
12.
EllgrenSMSpanoSMHurdYL (2007) Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology32: 607–615.
13.
EnnaceurADelacourJ (1988) A new one trial test for neurobiological studies of memory in rats: I. Behavioral data. Behav Brain Res31: 47–59.
14.
EnnaceurAMichalikovaSBradfordAAhmedS (2005) Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks. Behav Brain Res159: 247–266.
15.
FarhangBDiazSTangSLWagnerEJ (2009) Sex differences in the cannabinoid regulation of energy homeostasis. Psychoneuroendocrinology34Suppl 1: S237–S246.
16.
FerraroLTomasiniMCBeggiatoS. (2009) Short- and long-term consequences of prenatal exposure to the cannabinoid agonist WIN55,212-2 on rat glutamate transmission and cognitive functions. J Neural Transm116: 1017–1027.
17.
FileSE (1992) Behavioral detection of anxiolytic action. In: ElliotJMHealDJMarsdenCA (eds) Experimental Approaches to Anxiety and Depression. New York: Wiley, pp. 25–44.
18.
GonzálezSCascioMGFernández-RuizJFezzaFDi MarzoVRamosJA (2002) Changes in endocannabinoid contents in the brain of rats chronically exposed to nicotine, ethanol or cocaine. Brain Res954: 73–81.
19.
HerkenhamMLynnABJohnsonMR. (1991) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci11: 563–583.
IrvineEECheetaSFileSE (2001) Tolerance to nicotine’s effects in the elevated plus-maze and increased anxiety during withdrawal. Pharmacol Biochem Behav68: 319–325.
22.
JacobsenLKKrystalJHMenclWEWesterveldMFrostSJPughKR (2005) Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers. Biol Psychiatry57: 56–66.
23.
JacobsenLKMenclWEConstableRTWesterveldMPughKR (2007) Impact of smoking abstinence on working memory neurocircuitry in adolescent daily tobacco smokers. Psychopharmacology (Berl)193: 557–566.
24.
JacobsenLKPughKRConstableRTWesterveldMMenclWE (2006) Functional correlates of verbal memory deficits emerging during nicotine withdrawal in abstinent adolescent cannabis users. Biol Psychiatry61: 31–40.
25.
JohnstonALFileSE (1991) Sex differences in animal tests of anxiety. Physiol Behav49: 245–250.
26.
LamotaLBermudez-SilvaFJMarcoEM. (2008) Effects of adolescent nicotine and SR 147778 (Surinabant) administration on food intake, somatic growth and metabolic parameters in rats. Neuropharmacology54: 194–205.
27.
LarkinAEFaheyBGobboO. (2008) Blockade of NMDA receptors pre-training, but not post-training, impairs object displacement learning in the rat. Brain Res1199: 126–132.
28.
LevinEDMcClernonFJRezvaniAH (2006) Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology184: 523–539.
29.
LichtmanAHVarvelSAMartinBR (2002) Endocannabinoids in cognition and dependence. Prostaglandins Leukot Essent Fatty Acids66: 269–285.
30.
López-MorenoJAGonzález-CuevasGNavarroM (2007) The CB1 cannabinoid receptor antagonist rimonabant chronically prevents the nicotine-induced relapse to alcohol. Neurobiol Dis25: 274–283.
31.
López-MorenoJAGonzález-CuevasGRodríguez de FonsecaFNavarroM (2004) Long-lasting increase of alcohol relapse by the cannabinoid receptor agonist WIN 55,212-2 during alcohol deprivation. J Neurosci24: 8245–8252.
32.
LundqvistT (2005) Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions. Pharmacol Biochem Behav81: 319–330.
33.
MarcoEMGranstremOMorenoE. (2007) Subchronic nicotine exposure in adolescence induces long-term effects on hippocampal and striatal cannabinoid-CB1 and mu-opioid receptors in rats. Eur J Pharmacol557: 37–43.
34.
MarcoEMLlorenteRMorenoEBiscaiaJMGuazaCViverosMP (2006) Adolescent exposure to nicotine modifies acute functional responses to cannabinoid agonists in rats. Behav Brain Res172: 46–53.
35.
McGregorISIssakidisCNPriorG (1996) Aversive effects of the synthetic cannabinoid CP 55,940 in rats. Pharmacol Biochem Behav53: 657–664.
36.
MendrekAMonterossoJSimonSL. (2006) Working memory in cigarette smokers: comparison to non-smokers and effects of abstinence. Addict Behav31: 833–844.
37.
MitchellJBLaiaconaJ (1998) The medial frontal cortex and temporal memory: tests using spontaneous exploratory behaviour in the rat. Behav Brain Res97: 107–113.
38.
MugnainiMTessariMTarterGMerlo PichEChiamuleraCBunnemannB (2002) Upregulation of [3H]methyllycaconitine binding sites following continuous infusion of nicotine, without changes of alpha7 or alpha6 subunit mRNA: an autoradiography and in situ hybridization study in rat brain. Eur J Neurosci16: 1633–1646.
39.
NordentoftMHjorthøjC (2007) Cannabis use and risk of psychosis in later life. Lancet370: 293–294.
40.
O’SheaMMcGregorISMalletPE (2006) Repeated cannabinoid exposure during perinatal, adolescent or early adult ages produces similar long-lasting deficits in object recognition and reduced social interaction in rats. J Psychopharmacol20: 611–621.
41.
O’SheaMSinghMEMcGregorISMalletPE (2004) Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats. J Psychopharmacol18: 502–508.
42.
PaxinosGWatsonC (1997) The Rat Brain in Stereotaxic Coordinates, 3rd edn. San Diego: Academic Press.
43.
PellowSChopinPFileSEBrileyM (1985) Validation of open:closed arms entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods14: 149–167.
44.
PopeHGJrGruberAJHudsonJICohaneGHuestisMAYurgelun-ToddD (2003) Early-onset cannabis use and cognitive deficits: what is the nature of the association?Drug Alcohol Depend69: 303–310.
45.
PopeHGJrJacobsAMialetJPYurgelun-ToddDGruberS (1997) Evidence for a sex-specific residual effect of cannabis on visuospatial memory. Psychother Psychosom66: 179–184.
46.
ReichCGTaylorMEMcCarthyMM (2009) Differential effects of chronic unpredictable stress on hippocampal CB1 receptors in male and female rats. Behav Brain Res203: 264–269.
47.
Rodriguez de FonsecaFRamosJABonninAFernandez-RuizJJ (1993) Presence of cannabinoid binding sites in the brain from early postnatal ages. Neuroreport4: 135–138.
48.
RossatoJIBevilaquaLRMyskiwJCMedinaJHIzquierdoICammarotaM (2007) On the role of hippocampal protein synthesis in the consolidation and reconsolidation of object recognition memory. Learn Mem14: 34–46.
49.
RubinoTRealiniNBraidaD. (2009) Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus19: 763–772.
RubinoTViganòDRealiniN. (2008) Chronic delta 9 tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacology33: 2760–2771.
52.
SchneiderMKochM (2003) Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats. Neuropsychopharmacology28: 1760–1769.
53.
SchneiderMKochM (2007) The effect of chronic peripubertal cannabinoid treatment on deficient object recognition memory in rats after neonatal mPFC lesion. Eur Neuropsychopharmacol17: 180–186.
54.
SchneiderMSchömigELewekeFM (2008) Acute and chronic cannabinoid treatment differentially affects recognition memory and social behavior in pubertal and adult rats. Addict Biol13: 345–357.
55.
SemenovaSStolermanIPMarkouA (2007) Chronic nicotine administration improves attention while nicotine withdrawal induces performance deficits in the 5-choice serial reaction time task in rats. Pharmacol Biochem Behav87: 360–368.
56.
ShoaibMBizarroL (2005) Deficits in a sustained attention task following nicotine withdrawal in rats. Psychopharmacology178: 211–222.
57.
SlaweckiCJThorsellAEhlersCL (2004) Long-term neurobehavioral effects of alcohol or nicotine exposure in adolescent animal models. Ann N Y Acad Sci1021: 448–452.
58.
SolowijNBattistiR (2008) The chronic effects of cannabis on memory in humans: a review. Curr Drug Abuse Rev1: 81–98.
59.
SolowijNMichiePT (2007) Cannabis and cognitive dysfunction: parallels with endophenotypes of schizophrenia?. J Psychiatry Neurosci32: 30–52.
60.
SolowijNStephensRSRoffmanRA. (2002) Marijuana Treatment Project Research Group. Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA287: 1123–1131.
61.
SpearLP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev24: 417–463.
62.
StolermanIPMirzaNRHahnBShoaibM (2000) Nicotine in an animal model of attention. Eur J Pharmacol393: 147–154.
63.
SullivanJM (2000) Cellular and molecular mechanisms underlying learning and memory impairments produced by cannabinoids. Learn Mem7: 132–139.
64.
TrauthJASeidlerFJMcCookECSlotkinTA (1999) Adolescent nicotine exposure causes persistent upregulation of nicotinic cholinergic receptors in rat brain regions. Brain Res851: 9–19.
65.
TrezzaVCuomoVVanderschurenLJMJ (2008) Cannabis and the developing brain: Insights from behaviour. Eur J Pharmacol585: 441–452.
66.
ViverosMPLlorenteRMorenoEMarcoEM (2005) Behavioural and neuroendocrine effects of cannabinoids in critical developmental periods. Behav Pharmacol16: 353–362.
67.
ViverosMPMarcoEMFileSE (2006) Nicotine and cannabinoids: parallels, contrasts and interactions. Neurosci Biobehav Rev30: 1161–1181.
68.
ViverosMPMarcoEMLlorenteRLópez-GallardoM (2007) Endocannabinoid system and synaptic plasticity: implications for emotional responses. Neural Plast2007: 52908.
69.
WengerTGerendaiIFezzaF. (2002) The hypothalamic levels of the endocannabinoid, anandamide, peak immediately before the onset of puberty in female rats. Life Sci70: 1407–1414.
