Amphetamine Alters the Circadian Locomotor Activity Pattern of Adult WKY Female Rats

DOI: 10.4236/jbbs.2014.45022   PDF   HTML     2,605 Downloads   3,635 Views   Citations


There are no reports on the effect of amphetamine on female WKY circadian activity pattern. The objective of this study is to investigate whether repeated daily exposure to the psychostimulant amphetamine alters the locomotor circadian rhythm activity patterns of female adult Wistar-Kyoto (WKY) rats. Twenty-four rats were divided into two groups, control (N = 12) and experimental (N = 12), and kept in a 12:12 h light/dark cycle in an open field cage. After 5 to 7 days of acclimation, 11 days of consecutive non-stop recordings began. On experimental day 1, all groups were given an injection of saline. On experimental days 2 to 7, the experimental group was injected with 0.6 mg/kg amphetamine and the control group with saline followed by a washout phase from experimental day 8 to 10, and amphetamine re-challenge or saline on experimental day 11 similar to experimental day 2. Locomotor movements were determined using a computerized animal activity monitoring system, and cosine statistical analysis was used to fit a24-hour curve to the activity pattern. The horizontal activity (HA), total distance (TD), number of stereotypy (NOS), and stereotypical movements (SM) were analyzed for alterations in the circadian rhythm activity patterns. The data demonstrated that chronic amphetamine administration alters the mesor parameter of the circadian rhythm activity patterns, indicating that chronic amphetamine treatment exerts long term effects on these rats.

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Jones, C. , Yang, P. , Wilcox, V. and Dafny, N. (2014) Amphetamine Alters the Circadian Locomotor Activity Pattern of Adult WKY Female Rats. Journal of Behavioral and Brain Science, 4, 201-213. doi: 10.4236/jbbs.2014.45022.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Hechtman, L. (2000) Assessment and Diagnosis of Attention-Deficit/Hyperactivity Disorder. Child & Adolescent Psychiatric Clinics of North America, 9, 481-498.
[2] Mackworth, J.F. (1965) The Effect of Amphetamine on the Detectability of Signals in a Vigilance Task. Canadian Journal of Psychology, 19, 104-110.
[3] Evenden, J.L. and Robbins, T.W. (1985) The Effects of d-Amphetamine, Chlordiazepoxide and Alpha-Flupenthixol on Food-Reinforced Tracking of a Visual Stimulus by Rats. Psychopharmacology, 85, 360-366.
[4] Toon, S., Holt, B.L., Langley, S.J., Mullins, F.G.P., Rowland, M. and Halliday, M.S. (1990) Pharmacokinetic and Pharmacodynamic Interaction between the Antidepressant Tianeptine and Oxazepam at Steady-State. Psychopharmacology, 101, 226-232.
[5] Gray, J.D., Punsoni, M., Tabori, N.E., Melton, J.T., Fanslow, V., Ward, M.J., Zupan, B., Menzer, D., Rice, J., Drake, C.T., Romeo, R.D., Brake, W.G., Toress-Reveron, A. and Milner, T.A. (2007) Methylphenidate Administration to Juvenile Rats Alters Brain Areas Involved in Cognition, Motivated Behaviors, Appetite, and Stress. Journal of Neuroscience, 27, 7196-207.
[6] Scheving, L.E., Vedral, D.F. and Pauly, J.E (1968) Daily Circadian Rhythm in Rats to Damphetamine Sulphate: Effect of Binding and Continuous Illumination on the Rhythm. Nature, 219, 621-622.
[7] Uz, T., Akhisaroglu, M., Ahmed, R. and Manev, H. (2003) The Pineal Gland Is Critical for Circadian Period1 Expression in the Striatum and for Circadian Cocaine Sensitization in Mice. Neuropsychopharmacology, 28, 2117-23.
[8] Uz, T., Ahmed, R., Akhisaroglu, M., Kurtuncu, M., Imbesi, M., DirimArslan, A. and Manev, H. (2005) Effect of Fluoxetine and Cocaine on the Expression of Clock Genes in the Mouse Hippocampus and Striatum. Neuroscience, 134, 1309-1316.
[9] Gaytan, O., Ghelani, D., Martin, S., Swann, A. and Dafny, N. (1996) Dose-Response Characteristics of Methypehedate on Different Indices of Rats Locomotor Activity at the Beginning of the Dark Cycle. Brain Research, 727, 13-21.
[10] Gaytan, O., Swann, A.C. and Dafny, N. (1996) Effects of Amphetamine at the Beginning of the Light Cycle on Multiple Indices of Motor Activity in the Rat. European Journal of Pharmacology, 300, 1-8.
[11] Gaytan, O., Swann, A. and Dafny, N. (1998) Diurnal Differences in Rat’s Motor Response to Amphetamine. European Journal of Pharmacology, 345, 119-128.
[12] Gaytan, O., Yanga, P., Swann, A. and Dafny, N. (2000) Diurnal Differences in Sensitization to Methylphenidate. Brain Research, 864, 24-39.
[13] Melnick, S.M. and Dow-Edwards, D.L. (2001) Differential Behavioural Responses to Chronic Amphetamine in Adult Male and Female Rats Exposed to Postnatal Cocaine Treatment. Pharmacology, Biochemistry, and Behavior, 69, 219-224.
[14] Yang, P.B., Swann, A.C. and Dafny, N. (2003) Chronic Pretreatment with Methylphenidate Induces Cross-Sensitization with Amphetamine. Life Sciences, 73, 2899-2911.
[15] Yang, P.B., Swann, A.C. and Dafny, N. (2006) Acute and Chronic Methylphenidate Doseresponse Assessment on Three Adolescent Male Rat Strains. Brain Research, 71, 301-310.
[16] Dafny, N. and Yang, P.B. (2006) The Role of Age, Genotype, Sex, and Route of Acute and Chronic Administration of Methylphenidate: A Review of Its Locomotor Effects. Brain Research Bulletin, 68, 393-405.
[17] Gaytan, O., Lewis, C., Swann, A. and Dafny, N. (1999) Diurnal Differences in Amphetamine Sensitization. European Journal of Pharmacology, 374, 1-9.
[18] Algahim, M.F., Yang, P.B., Wilcox, V.T., Burau, K.D., Swann, A.C. and Dafny, N. (2009) Prolonged Methylphenidate Treatment Alters the Behavioral Diurnal Activity Pattern of Adult Male Sprague-Dawley Rats. European Journal of Pharmacology, 92, 93-99.
[19] Lee, M.J., Yang, P.B., Wilcox, V.T., Burau, K.D., Swann, A.C. and Dafny, N. (2009) Does Repetitive Ritalin Injection Produce Long-Term Effects on SD Female Adolescent Rats? Neuropharmacology, 57, 201-207.
[20] Dafny, N. and Terkel, J. (1990) Hypothalamic Neuronal Activity Associated with Onset of Pseudopregnancy in the Rat. Neuroendocrinology, 51, 459-467.
[21] Bingham, C., Arbogast, B., Guillaume, G.C., Lee, J.K. and Halberg F. (1982) Inferential Statistical Methods for Estimating and Comparing Cosinor Parameters. Chronobiologia, 9, 397-439.
[22] Kurtuncu, M., Arslan, A., Akhisaroglu, M., Manev, H. and Uz, T. (2004) Involvement of the Pineal Gland in Diurnal Cocaine Reward in Mice. European Journal of Pharmacology, 489, 203-205.
[23] Moore, R.Y. (1983) Organization and Function of a Central Nervous System Circadian Oscillator: The Suprachiasmatic Hypothalamic Nucleus. Federation Proceedings, 42, 2783-2789.
[24] Minors, D.S. and Waterhouse, J.M. (1986) Circadian Rhythms and Their Mechanisms. Experientia, 42, 1-13.
[25] Reppert, S.M. and Weaver, D.R. (2002) Coordination of Circadian Timing in Mammals. Nature, 418, 935-941.
[26] Gachon, F., Nagoshi, E., Brown, S.A., Ripperger, J. and Schibler, U. (2004) The Mammalian Circadian Timing System: From Gene Expression to Physiology. Chromosoma, 113, 103-112.
[27] Brandon, C.L., Marinelli, M., Baker, L.K. and White, F.J. (2001) Enhanced Reactivity and Vulnerability to Cocaine Following Methylphenidate Treatment in Adolescent Rats. Neuropsychopharmacology, 25, 651-661.
[28] Segal, D.S. and Kuczenski, R. (2006) Human Methamphetamine Pharmacokinetics Simulated in the Rat: Single Daily Intravenous Administration Reveals Elements of Sensitization and Tolerance. Neuropsychopharmacology, 31, 941-955.
[29] Barrett, R.J., Caul, W.F. and Smith, R. (2005) Withdrawal, Tolerance, and Sensitization to Dopamine Mediated Interoceptive Cues in Rats Trained on a Three-Lever Drug-Discrimination Task. Pharmacology Biochemistry and Behavior, 81, 1-8.
[30] Fleckenstein, A.E. and Hanson, G.R. (2003) Impact of Psychostimulants on Vesicular Monoamine Transporter Function. European Journal of Pharmacology, 479, 283-289.
[31] Pontieri, F.E., Tanda, G. and Chiara, G.D. (1995) Intravenous Cocaine, Morphine, and Amphetamine Preferentially Increase Extracellular Dopamine in the “Shell” as Compared with the “Core” of the Rat Nucleus Accumbens. Proceedings of the National Academy of Sciences of the United States of America, 92, 12304-12308.
[32] Paulson, P.E. and Robinson, T.E. (1996) Regional Differences in the Effects of Amphetamine Withdrawal on Dopamine Dynamics in the Striatum. Analysis of 21 Circadian Patterns Using Automated Online Microdialysis. Neuropsychopharmacology, 14, 325-337.
[33] Shuster, L., Hudson, J., Anton, M. and Righi, D. (1982) Sensitization of Mice to Methylphenidate. Psychopharmacologia, 77, 31-36.
[34] Chao, J. and Nestler, E.J. (2004) Molecular Neurobiology of Drug Addiction. Annual Review of Medicine, 55, 113-132.
[35] Nestler, E.J. (2004) Molecular Mechanisms of Drug Addiction. Neuropharmacology, 47, 24-32.
[36] Kosobud, A., Gillman, A., Leffel, J., Pecoraro, N., Rebec, G. and Timberlake, W. (2007) Drugs of Abuse Can Entrain Circadian Rhythms. The Scientific World Journal, 7, 203-212.
[37] White, W. and White, I.M. (2006) An Activity Indicator of Acute Withdrawal Depends on Amphetamine Dose in Rats. Physiology & Behavior, 87, 368-376.
[38] Gordon, H. (2007) Sleep, Circadian Rhythm, and Drug Abuse. The Scientific World Journal, 7, 191-193.
[39] McClung, C. (2007) Circadian Rhythms, the Mesolimbic Dopaminergic Circuit, and Drug Addiction. The Scientific World Journal, 7, 194-202.
[40] Lee, M.J., Burau, K.D. and Dafny, N. (2013) Behavioral Daily Rhythmic Activity Pattern of Adolescent Female Rat Is Modulated by Acute and Chronic Cocaine. Journal of Neural Transmission, 120, 733-744.
[41] Lee, M.J., Yang, P.B., Wilcox, V.T., Burau, K.D., Swann, A.C. and Dafny, N. (2009) Does Repetitive Ritalin Injection Produce Long-Term Effects on SD Female Adolescent Rats? Neuropharmacology, 57, 201-207.
[42] Algahim, M.F., Yang, P.B., Burau, K.D., Swann, A.C. and Dafny, N. (2010) Repetitive Ritalin Treatment Modulates the Diurnal Activity Pattern of Young SD Male Rats. Central Nervous System Agents in Medicinal Chemistry, 10, 1-11.
[43] Russo, S.J., Dietz, D.M., Damitriu, D. Morrison, J.H., Malenka, R.C. and Nestler, E.J. (2010) The Addicted Synapse: Mechanism of Synaptic and Structural Plasticity in Nucleus Accumbens. Trends in Neurosciences, 33, 267-276.

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