Abstract
Exposure to early life stress has been suggested to increase an individual’s vulnerability to methamphetamine (MA) dependence. Although there is no cure for drug dependence, the opioid and vesicular monoamine transporter 2 (VMAT2) systems may be useful targets for treatment insofar as they play pivotal roles in the neurochemistry of addiction. Here we investigated the effects of naltrexone (opioid antagonist) and lobeline (VMAT2 inhibitor) on MA-induced place preference in adolescent rodents subjected to early life trauma (maternal separation, MS) and controls, as well as the effects on dopamine and serotonin levels in the striatum. We found: (1) maternal separation attenuated methamphetamine-induced place preference; (2) lobeline and naltrexone treatment had differential effects on serotonin and dopamine concentrations in the striatum, naltrexone increased serotonin levels in the maternally separated animals. The hypothesized effect of early adversity increasing MA-induced place preference may not be apparent in adolescence. However the data are consistent with the hypothesis that early life stress influences neurochemical pathways that predispose an individual to drug dependence.
References
Adriani W, Laviola G (2002) Spontaneous novelty seeking and amphetamine-induced conditioning and sensitization in adult mice: evidence of dissociation as a function of age at weaning. Neuropsychopharmacology 27:225–236. doi:10.1038/S0893-133X(02)00300-7
Anggadiredja K, Sakimura K, Hiranita T, Yamamoto T (2004) Naltrexone attenuates cue- but not drug-induced methamphetamine seeking: a possible mechanism for the dissociation of primary and secondary reward. Brain Res 1021:272–276. doi:10.1016/j.brainres.2004.06.051
Balcells-Olivero M, Vezina P (1997) Effects of naltrexone on amphetamine-induced locomotion and rearing: acute and repeated injections. Psychopharmacol (Berl) 131:230–238. doi:10.1007/s002130050288
Benwell MEM, Balfour DJK (1998) The influence of lobeline on nucleus accumbens dopamine and locomotor responses to nicotine in nicotine-pretreated rats. Br J Pharmacol 125:1115–1119. doi:10.1038/sj.bjp.0702161
Bergevin A, Girardot D, Bourque MJ, Trudeau LE (2002) Presynaptic mu-opioid receptors regulate a late step of the secretory process in rat ventral tegmental area GABAergic neurons. Neuropharmacology 42:1065–1078. doi:10.1016/S0028-3908(02)00061-8
Bjork JM, Smith AR, Chen G, Hommer DW (2010) Adolescents, adults and rewards: comparing motivational neurocircuitry recruitment using fMRI. PLoS One 5:e11440. doi:10.1371/journal.pone.0011440
Boasen JF, McPherson RJ, Hays SL, Juul SE, Gleason CA (2009) Neonatal stress or morphine alters adult mouse conditioned place preference. Neonatology 95:230–239. doi:10.1159/000165379
Brebner K, Ahn S, Phillips AG (2005) Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates. Psychopharmacol (Berl) 177:409–417. doi:10.1007/s00213-004-1968-6
Brodie MS, Bunney EB (1996) Serotonin potentiates dopamine inhibition of ventral tegmental area neurons in vitro. J Neurophysiol 76:2077–2082
Chiu CT, Ma T, Ho IK (2005) Attenuation of methamphetamine-induced behavioral sensitization in mice by systemic administration of naltrexone. Brain Res Bull 67:100–109. doi:10.1016/j.brainresbull.2005.05.028
Chiu CT, Ma T, Ho IK (2006) Methamphetamine-induced behavioral sensitization in mice: alterations in μ-opioid receptor. J Biomed Sci 13:797–811. doi:10.1007/s11373-006-9102-x
Di Chara G, North AR (1992) Neurobiology of opiate abuse. Trends Pharmacol Sci 13:185–193
Di Matteo V, De Blasi A, Di Giulio C, Esposito E (2001) Role of 5-HT(2C) receptors in the control of central dopamine function. Trends Pharmacol Sci 22:229–232. doi:10.1016/S0165-6147(00)01688-6
Dinwiddie SH, Reich T, Cloninger CR (1992) Prediction of intravenous drug use. Compr Psychiatry 33:173–179. doi:10.1016/0010-440X(92)90026-M
Dwoskin LP, Crooks PA (2002) A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse. Biochem Pharmacol 63:89–98. doi:10.1016/S0006-2952(01)00899-1
Ettenberg A, Pettit HO, Bloom FE, Koob GF (1982) Heroin and cocaine intravenous self-administration in rats: mediation by separate neural systems. Psychopharmacol (Berl) 78:204–209
Eyerman DJ, Yamamoto BK (2005) Lobeline attenuates methamphetamine-induced changes in vesicular monoamine transporter 2 immunoreactivity and monoamine depletions in the striatum. J Pharmacol Exp Ther 312:160–169. doi:10.1124/jpet.104.072264
Gawin FH (1991) Cocaine addiction: psychology and neurophysiology. Science 251:1580–1586. doi:10.1126/science.2011738
Gordon HW (2002) Early environmental stress and biological vulnerability to drug abuse. Psychoneuroendocrinology 27:115–126. doi:10.1016/S0306-4530(01)00039-7
Gutierres SE, Molof M, Ungerleider S (1994) Relationship of “risk” factors to teen substance use: a comparison of abstainers, infrequent users, and frequent users. Int J Addict 12:1047–1056
Häggkvist J, Lindholm S, Franck J (2009) The opioid receptor antagonist naltrexone attenuates reinstatement of amphetamine drug-seeking in the rat. Behav Brain Res 197:219–224. doi:10.1016/j.bbr.2008.08.021
Häggkvist J, Björkholm C, Steensland P, Lindholm S, Franck J, Schilström B (2011) Naltrexone attenuates amphetamine-induced lcomotor sensitization in the rat. Addict Biol 16:20–29. doi:10.1111/j.1369-1600.2009.00199.x
Harrigan SE, Downs DA (1978) Continuous intravenous naltrexone effects on morphine self-administration in rhesus monkeys. J Pharmacol Exp Ther 204:481–485
Harrod SB, Dwoskin LP, Crooks PA, Klebaur JE, Bardo MT (2001) α-Lobeline attenuates D-methamphetamine self-administration in rats. J Pharmacol Exp Ther 298:172–179
Harrod SB, Dwoskin LP, Green TA, Gehrke BJ, Bardo MT (2003) Lobeline does not serve as a reinforcer in rats. Psychopharmacol (Berl) 165:397–404. doi:10.1007/s00213-002-1289-6
Hays SL, McPherson RJ, Juul SE, Wallace G, Schindler AG, Chavkin C, Gleason CA (2012) Long-term effects of neonatal stress on adult conditioned place preference (CPP) on hippocampal neurogenesis. Behav Brain Res 227:7–11. doi:10.1016/j.bbr.2011.10.033
Hemby SE, Smith JE, Dworkin SI (1996) The effects of eticlopride and naltrexone on responding maintained by food, cocaine, heroin and cocaine/heroin combinations in rats. J Pharmacol Exp Ther 277:1247–1258
Holtzman SG (1990) Discriminative stimulus effects of drugs: relationship to potential for abuse. In: Adler MW, Cowan A (eds) Testing and evaluation of drugs of abuse, modern methods in pharmacology. Wiley-Liss, New York, pp 193–210
Hooks MS, Jones DN, Justice JB Jr, Holtzman SG (1992) Naloxone reduces amphetamine-induced stimulation of locomotor activity and in vivo dopamine release in the striatum and nucleus accumbens. Pharmacol Biochem Behav 42:765–770
Hubner CB, Bain GT, Kornetsky C (1987) The combined effects of morphine and D-amphetamine on the threshold for brain stimulation reward. Pharmacol Biochem Behav 28:311–315. doi:10.1016/0091-3057(87)90230-9
Huot RL, Plotsky PM, Lenox RH, McNamara RK (2002) Neonatal maternal separation reduces hippocampal mossy fiber density in adult Long Evans rats. Brain Res 950:52–63
Infurna RN, Spear LP (1979) Developmental changes in amphetamine-induced taste aversions. Pharmacol Biochem Behav 11:31–35
Ivy AS, Rex CS, Chen Y, Dubé C, Maras PM, Grigoriadis DE, Gall CM, Lynch G, Baram TZ (2010) Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors. J Neurosci 30:13005–13015. doi:10.1523/JNEUROSCI.1784-10.2010
Johnson SW, North RA (1992) Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 12:483–488
Kalivas PW, Stewart J (1991) Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Rev 16:223–244
Kerstetter KA, Kantak KM (2007) Differential effects of self-administered cocaine in adolescent and adult rats on stimulus-reward learning. Psychopharmacology 194:403–411. doi:10.1007/s00213-007-0852-6
Kilbourn M, Lee L, Borght TV, Jewett D, Frey K (1995) Binding of α-dihydrotetrabenazine to the vesicular monoamine transporter is stereoselective. Eur J Pharmacol 278:249–252. doi:10.1016/0014-2999(95)00162-E
Korosi A, Naninck EFG, Oomen CA, Schouten M, Krugers H, Fitzsimons C, Lucassen PJ (2012) Early-life stress mediated modulation of adult neurogenesis and behaviour. Behav Brain Res 227:400–409. doi:10.1016/j.bbr.2011.07.037
Ladd CO, Huot RL, Thrivikraman KV, Nemeroff CB, Meaney MJ, Plotsky PM (2000) Long-term behavioural and neuroendorine adaptations to adverse early experience. In: Mayer EA, Saper CB (eds) Progress in brain research: the biological basis for mind body interactions. Elsevier, Amsterdam, pp 81–103
Laviola G, Adriani W, Terranova ML, Gerra G (1999) Psychobiological risk factors for vulnerability to psychostimulants in human adolescents and animal models. Neurosci Biobehav Rev 23:993–1010. doi:10.1016/S0149-7634(99)00032-9
Lecca D, Shim I, Costa E, Javaid JI (2000) Striatal application of nicotine, but not of lobeline, attenuates dopamine release in freely moving rats. Neuropharmacology 39:88–98. doi:10.1016/S0028-3908(99)00085-4
Lendvai B, Sershen H, Lajtha A, Santha E, Baranyi M, Vizi ES (1996) Differential mechanisms involved in the effect of nicotinic agonists DMPP and lobeline to release [3H]5-HT from rat hippocampal slices. Neuropharmacology 35:1769–1777. doi:10.1016/S0028-3908(96)00115-3
Leone P, Poddock D, Wise RA (1991) Morphine-dopamine interaction: ventral tegmental morphine increases nucleus accumbens dopamine release. Pharmacol Biochem Behav 39:469–472. doi:10.1016/0091-3057(91)90210-S
Liu Y, Peter D, Merickel A, Krantz D, Finn PJ, Edwards RH (1996) A molecular analysis of vesicular amine transporter. Behav Brain Res 73:51–58
Matthews K, Robbins TW (2003) Early experience as a determinant of adult behavioural responses to reward: the effects of repeated maternal separation in the rat. Neurosci Biobehav Rev 27:45–55. doi:10.1016/S0149-7634(03)00008-3
Meaney MJ, Brake W, Gratton A (2002) Environmental regulation of the development of mesolimbic dopamine systems: a neurobiological mechanism for vulnerability to drug abuse? Psychoneuroendocrinology 27:127–138. doi:10.1016/S0306-4530(01)00040-3
Miller DK, Crooks PA, Dwoskin LP (2000) Lobeline inhibits nicotine-evoked [3H]dopamine overflow from rat striatal slices and nicotine-evoked 86Rb+ efflux from thalamic synaptosomes. Neuropharmacology 39:2654–2662. doi:10.1016/S0028-3908(00)00140-4
Miller DK, Crooks PA, Teng L, Witkin JM, Munzar P, Goldberg SR, Acri JB, Dwoskin LP (2001) Lobeline inhibits the neurochemical and behavioral effects of amphetamine. J Pharmacol Exp Ther 296:1023–1034
Negus SS, Mello NK, Portoghese PS, Lukas SE, Mendelson JH (1995) Role of δ-opioid receptors in the reinforcing and discriminative stimulus effects of cocaine in rhesus monkeys. J Pharmacol Exp Ther 273:1245–1256
Olive MF, Koenig HN, Nannini MA, Hodge CW (2001) Stimulation of endorphin neurotransmission in the nucleus accumbens by ethanol, cocaine and amphetamine. J Neurosci 21:RC184
Pifl C, Drobny H, Reither H, Hornykiewicz O, Singer EA (1995) Mechanism of the dopamine-releasing actions of amphetamine and cocaine: plasmalemmal dopamine transporter versus vesicular monoamine transporter. Mol Pharmacol 47:368–373
Rada P, Mark GP, Pothos E, Hoebel BG (1991) Systemic morphine simultaneously decreases extracellular acetylcholine and increases dopamine in the nucleus accumbens of freely moving rats. Neuropharmacology 30:1133–1136
Ramsey NF, Van Ree JM (1990) Chronic pretreatment with naltrexone facilitates acquisition of intravenous cocaine self-administration in rats. Eur Neuropsychopharmacol 1:55–61
Schad CA, Justice JB, Holtzman SG (1995) Naloxone reduces the neurochemical and behavioral effects of amphetamine but not those of cocaine. Eur J Pharmacol 275:9–16. doi:10.1016/0014-2999(94)00726-N
Schad CA, Justice JB Jr, Holtzman SG (1996) Differential effects of delta- and mu-opioid receptor antagonists on the amphetamine-induced increase in extracellular dopamine in striatum and nucleus accumbens. J Neurochem 67:2292–2299. doi:10.1046/j.1471-4159.1996.67062292.x
Scherman D, Boschi G, Rips R, Henry JP (1986) The regionalization of [3H]dihydrotetrabenazine binding sites in the mouse brain and its relationship to the distribution of monoamines and their metabolites. Brain Res 370:176–181. doi:10.1016/0006-8993(86)91120-0
Schuster CR, Johanson CE (1988) Relationship between the discriminative stimulus properties and subjective effects of drugs. In: Colpaert FC, Balster RL (eds) Psychopharmacology, Series 4: transduction mechanisms of drug stimuli. Springer, Berlin, pp 161–175
Shimosato K, Ohkuma S (2000) Simultaneous monitoring of conditioned place preference and locomotor sensitization following repeated administration of cocaine and methamphetamine. Pharmacol Biochem Behav 66:285–292. doi:10.1016/S0091-3057(00)00185-4
Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacol (Berl) 158:343–359. doi:10.1007/s002130100917
Spanagel R, Weiss F (1999) The dopamine hypothesis of reward: past and current status. Trends Neurosci 22:521–527. doi:10.1016/S0166-2236(99)01447-2
Spanagel R, Herz A, Shippenberg TS (1992) Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci USA 2046–2050
Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463. doi:10.1016/S0149-7634(00)00014-2
Stolerman IP, Garcia HS, Mirza NR (1995) Dissociation between locomotor stimulant and depressant effects of nicotine agonists in rats. Psychopharmacol (Berl) 117:430–437
Sulzer D, Rayport S (1990) Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules: a mechanism of action. Neuron 5:797–808. doi:10.1016/0896-6273(90)90339-H
Sulzer D, Sonders MS, Poulsen NW, Galli A (2005) Mechanisms of neurotransmitter release by amphetamine: a review. Prog Neurobiol 75:406–433. doi:10.1016/j.pneurobio.2005.04.003
Takahashi N, Miner LL, Sora I, Ujike H, Revay RS, Kostic V, Jackson-Lewis V, Przedborski S, Uhl GR (1997) VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity. Proc Natl Acad Sci USA 94:9938–9943
Tatsuta T, Kitanaka N, Kitanaka J, Morita Y, Takemura M (2006) Lobeline attenuates methamphetamine-induced stereotypy in adolescent mice. Neurochem Res 31:1359–1369. doi:10.1007/s11064-006-9180-1
Teng LH, Crooks PA, Sonsalla PK, Dwoskin LP (1997) Lobeline and nicotine evoke [3H]overflow from rat striatal slices preloaded with [3H]dopamine: differential inhibition of synaptosomal and vesicular [3H]dopamine uptake. J Pharmacol Exp Ther 280:1432–1444
Terry AV, Williamson R, Gattu M, Beach JW, McCurdy CR, Sparks JA, Pauly JR (1998) Lobeline and structurally simplified analogs exhibit differential agonist activity and sensitivity to antagonist blockade when compared to nicotine. Neuropharmacology 37:93–102. doi:10.1016/S0028-3908(97)00142-1
Tirelli E, Laviola G, Adriani W (2003) Ontogenesis of behavioral sensitization and conditioned place preference induced by psychostimulants in laboratory rodents. Neurosci Biobehav Rev 27:163–178. doi:10.1016/s0149-7634(03)00018-6
United Nations Office on Drugs and Crime (2003) Ecstasy and amphetamines, Global Survey 2003. United Nations, New York
Uwai K, Uchiyama H, Sakurada S, Kabuto C, Takeshita M (2004) Syntheses and receptor-binding studies of derivatives of the opioid antagonist naltrexone. Bioorg Med Chem 12:417–421. doi:10.1016/j.bmc.2003.10.039
Wilhelm CJ, Johnson RA, Lysko PG, Eshleman AJ, Janowsky A (2004) Effects of methamphetamine and lobeline on vesicular monoamine and dopamine transporter-mediated dopamine release in a cotransfected model system. J Pharmacol Exp Ther 310:1142–1151. doi:10.1124/jpet.104.067314
Wilhelm CJ, Johnson RA, Eshleman AJ, Janowsky A (2008) Lobeline effects on tonic and methamphetamine-induced dopamine release. Biochem Pharmacol 75:1411–1415. doi:10.1016/j.bcp.2007.11.019
Winger G, Skjoldager P, Woods JH (1992) Effects of buprenorphine and other opioid agonists and antagonists on alfentanil- and cocaine-reinforced responding in rhesus monkeys. J Pharmacol Exp Ther 261:311–317
Winslow JT, Miczek KA (1988) Naltrexone blocks amphetamine-induced hyperactivity, but not disruption of social and agonistic behavior in mice and squirrel monkeys. Psychopharmacol (Berl) 96:493–499
Yu L, Kuo YM, Cherng CFG (2001) Opioid peptides alleviate while naloxone potentiated methamphetamine-induced striatal dopamine depletion in mice. J Neural Transm 108:1231–1237. doi:10.1007/s007020100001
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This work was supported by the Medical Research Council (MRC) of South Africa.
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Dimatelis, J.J., Russell, V.A., Stein, D.J. et al. The effects of lobeline and naltrexone on methamphetamine-induced place preference and striatal dopamine and serotonin levels in adolescent rats with a history of maternal separation. Metab Brain Dis 27, 351–361 (2012). https://doi.org/10.1007/s11011-012-9288-8
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DOI: https://doi.org/10.1007/s11011-012-9288-8