The dorsal striatum is the main input structure of the basal ganglia and the major target area of dopaminergic projections originating in the substantia nigra pars compacta. Heavily involved in the regulation of voluntary movement and habit formation, this structure is of strong importance in Parkinson's disease, obsessive-compulsive disorder, Tourette's syndrome and addiction. The C57/Bl6J mouse strain, the most commonly used strain in preclinical research today, is frequently used as a model organism for analysis of dopaminergic parameters implicated in human pathophysiology. Several components of the dopamine system have been shown to vary with age and sex, however knowledge of the contribution of these factors for dopamine release kinetics in the C57/Bl6J mouse strain is lacking. In the present study, we used an intracranial KCl-stimulation challenge paradigm to provoke release from dopaminergic terminals in the dorsal striatum of anaesthetized C57/Bl6J mice. By high-speed in vivo chronoamperometric recordings, we analyzed DA release parameters in male and female mice of two different ages. Our experiments demonstrate elevated DA amplitudes in adult compared to young mice of both sexes and higher DA amplitudes in females compared to males at both ages. Adult mice exhibited higher recovery capabilities after repeated stimulation than did young mice and also showed a lower variability in the kinetic parameters trise and t80 between stimulations. These results identified age- and sex- dimorphisms in DA release parameters and point to the importance of taking these dimorphisms into account when utilizing the C57/Bl6J mouse strain as model for neurological and neuropsychiatric disorders.
References
[1]
Andén NE, Carlsson A, Dahlstr？m A, Fuxe K, Hillarp N？, et al. (1964) Demonstration and mapping out of nigro-neostriatal dopamine neurons. Life Sciences 3: 523–530.
[2]
Obeso JA, Rodríguez-Oroz MC, Benitez-Temino B, Blesa FJ, Guridi J, et al. (2008) Functional organization of the basal ganglia: Therapeutic implications for Parkinson's disease. Movement Disorders 23: S548–S559.
[3]
Yin HH, Knowlton BJ (2006) The role of the basal ganglia in habit formation. Nature Reviews Neuroscience 7: 464–476.
[4]
Baldan Ramsey LC, Xu M, Wood N, Pittenger C (2011) Lesions of the dorsomedial striatum disrupt prepulse inhibition. Neuroscience 180: 222–228.
[5]
Wightman RM, Robinson DL (2002) Transient changes in mesolimbic dopamine and their association with 'reward'. J Neurochem 82: 721–735.
[6]
Rios M, Habecker B, Sasaoka T, Eisenhofer G, Tian H, et al. (1999) Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase. J Neurosci 19: 3519–3526.
[7]
Ciliax BJ, Heilman C, Demchyshyn LL, Pristupa ZB, Ince E, et al. (1995) The dopamine transporter: immunochemical characterization and localization in brain. J Neurosci 15: 1714–1723.
[8]
Peter D, Liu Y, Sternini C, de Giorgio R, Brecha N, et al. (1995) Differential expression of two vesicular monoamine transporters. J Neurosci 15: 6179–6188.
[9]
Elsworth JD, Roth RH (1997) Dopamine Synthesis, Uptake, Metabolism, and Receptors: Relevance to Gene Therapy of Parkinson's Disease. Experimental Neurology 144: 4–9.
[10]
Riccardi P, Li R, Ansari MS, Zald D, Park S, et al. (2006) Amphetamine-induced displacement of [18F] fallypride in striatum and extrastriatal regions in humans. Neuropsychopharmacology 31: 1016–1026.
[11]
Walker QD, Rooney MB, Wightman RM, Kuhn CM (1999) Dopamine release and uptake are greater in female than male rat striatum as measured by fast cyclic voltammetry. Neuroscience 95: 1061–1070.
[12]
Ji J, McDermott JL, Dluzen DE (2007) Sex differences in K+-evoked striatal dopamine output from superfused striatal tissue fragments of reserpine-treated CD-1 mice. J Neuroendocrinol 19: 725–731.
[13]
Stamford JA (1989) Development and ageing of the rat nigrostriatal dopamine system studied with fast cyclic voltammetry. Journal of neurochemistry 52: 1582–1589.
[14]
Nakano M, Oenzil F, Mizuno T, Gotoh S (1995) Age-related changes in the lipofuscin accumulation of brain and heart. Gerontology 41 Suppl 2: 69–79.
[15]
Kumar V, Kim K, Joseph C, Kourrich S, Yoo SH, et al. (2013) C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates cocaine response. Science 342: 1508–1512.
[16]
Gerhardt GA, Rose GM, Hoffer BJ (1986) Release of monoamines from striatum of rat and mouse evoked by local application of potassium: evaluation of a new in vivo electrochemical technique. J Neurochem 46: 842–850.
[17]
Alsi？ J, Nordenankar K, Arvidsson E, Birgner C, Mahmoudi S, et al. (2011) Enhanced sucrose and cocaine self-administration and cue-induced drug seeking after loss of VGLUT2 in midbrain dopamine neurons in mice. The Journal of neuroscience: the official journal of the Society for Neuroscience 31: 12593–12603.
[18]
Dluzen De, McDermott Jl (2008) Sex Differences in Dopamine- and Vesicular Monoamine-Transporter Functions. Annals of the New York Academy of Sciences 1139: 140–150.
[19]
Borland LM, Michael AC (2007) An Introduction to Electrochemical Methods in Neuroscience. In: Michael AC, Borland LM, editors. Electrochemical Methods for Neuroscience. Boca Raton (FL).
[20]
Friedemann MN, Gerhardt GA (1992) Regional effects of aging on dopaminergic function in the Fischer-344 rat. Neurobiol Aging 13: 325–332.
[21]
Gerhardt GA, Oke AF, Nagy G, Moghaddam B, Adams RN (1984) Nafion-coated electrodes with high selectivity for CNS electrochemistry. Brain research 290: 390–395.
[22]
Paxinos G (2004) The mouse brain in stereotaxic coordinates: Gulf Professional Publishing.
[23]
Reith ME, Xu C, Chen NH (1997) Pharmacology and regulation of the neuronal dopamine transporter. European journal of pharmacology 324: 1–10.
[24]
Michael AC, Ikeda M, Justice JB Jr (1987) Mechanisms contributing to the recovery of striatal releasable dopamine following MFB stimulation. Brain Research 421: 325–335.
[25]
Cosgrove KP, Mazure CM, Staley JK (2007) Evolving knowledge of sex differences in brain structure, function, and chemistry. Biological psychiatry 62: 847–855.
[26]
Lavalaye J, Booij J, Reneman L, Habraken JB, van Royen EA (2000) Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers. European journal of nuclear medicine 27: 867–869.
[27]
Laakso A, Vilkman H, Bergman J, Haaparanta M, Solin O, et al. (2002) Sex differences in striatal presynaptic dopamine synthesis capacity in healthy subjects. Biol Psychiatry 52: 759–763.
[28]
H？fner H (2003) Gender differences in schizophrenia. Psychoneuroendocrinology 28 Suppl 2: 17–54.
[29]
Karayiorgou M, Altemus M, Galke BL, Goldman D, Murphy DL, et al. (1997) Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder. Proc Natl Acad Sci U S A 94: 4572–4575.
[30]
Bruun RD, Budman CL (1997) The course and prognosis of Tourette syndrome. Neurologic clinics 15: 291–298.
[31]
Shulman LM (2007) Gender differences in Parkinson's disease. Gender medicine 4: 8–18.
