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Cocaine as Opposed to Methamphetamine Did not Restore CirWadian Activity Rhythms in Arrhythmic Suprachiasmatic Nucleus Lesioned C3H/HeN Mice when Paired with Running Wheel
Author(s) -
Vega Juliany Yari Marrero,
Clough Shan,
Dubocovich Margarita L
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.813.3
Subject(s) - circadian rhythm , suprachiasmatic nucleus , methamphetamine , medicine , endocrinology , light effects on circadian rhythm , dopamine , period (music) , circadian clock , rhythm , premovement neuronal activity , neuroscience , chemistry , biology , physics , acoustics
The “master biological clock” or suprachiasmatic nucleus (SCN) orchestrates synchrony among central and peripheral circadian oscillators. When the SCN is removed the circadian rhythm of an organism becomes arrhythmic. However, when methamphetamine (Meth), a psychostimulant, is given to mice ad libitium in drinking water, it rescues the locomotor behavioral rhythms in arrhythmic SCN lesioned (SCNX) mice ( Tataroglu et al., JBiol Rhythms 2006;21;185–94 ). We recently demonstrated that Meth, which increases dopamine release by reversing the neuronal transporter, paired with concurrent access to running wheel (RW), is necessary for the expression of circadian entrainment in SCNX mice, possibly by activating an extra‐SCN brain oscillator ( Rawashdeh et al. FASEB J, 2016 ). The goal of our project was to determine the ability of another psychostimulant, cocaine, which increases depolarization‐evoked dopamine release by blocking neuronal uptake, to establish rhythmic circadian activity in SCNX mice. Following the protocol described by Rawashdeh et al., 2016, C3H/HeN male mice (3–4 months old) underwent sham surgery (n=8) or SCN electrolytic lesions (n=11) (SCNX). Sham operated (free running circadian rhythms) and SCNX (arrhythmic) mice in constant dark were given a single daily vehicle (0.9% saline, i.p.) or cocaine (20 mg/kg, i.p.) injection at the beginning of an 8‐hour period of restricted RW access, for 14 days. Mice were then provided a 7‐day period of continuous access to RW to assess the development of a free running circadian activity rhythm. Our results demonstrate that SCNX mice treated for 14 days with either vehicle or cocaine paired with RW did not develop rhythmic circadian activity. This is in contrast to Meth, which when used in the same paradigm, induced a free‐running rhythm in SCNX mice (Rawashdeh et al., 2016). Although both Meth and cocaine, at doses that elicit similar levels of locomotor activity, increase the extracellular concentration of dopamine in the striatum and nucleus accumbens, the net levels of extracellular dopamine are 2–3 times fold higher following treatment with Meth (reversal of dopamine transporter) than with cocaine (blockade of neuronal uptake) ( Kuczenski, et al., J Neurosci 1991;11; 2703–12 ). We suggest that increased level of synaptic dopamine induced by Meth paired with RW compared to cocaine may be necessary to re entrain circadian activity rhythms in arrhythmic mice. Support or Funding Information S upported by JSMBS funds to MLD