Share This Article:

Effect of Chronic DL-Amphetamine Exposure on Brain Volume, Anxiogenic, Locomotor, and Social Behaviors in Male SD Rats

Abstract Full-Text HTML XML Download Download as PDF (Size:1075KB) PP. 375-383
DOI: 10.4236/jbbs.2014.48036    2,929 Downloads   3,662 Views  

ABSTRACT

Research examining the long-term effects of drugs such as AdderallTM, a mixed DL-amphetamine, as a first-line treatment strategy for those diagnosed with attention deficit hyperactivity disorder (ADHD), is very much lacking. In order to address this, the present study sought to examine possible behavioral and neuroanatomical effects of chronic oral exposure to DL-amphetamine administered at a relatively low dose to the developing male Sprague Dawley rat. Animals were administered a mixture of chocolate drink and DL-amphetamine at a dose of 1.6 mg/kg for 36 days, beginning at PD 24 and ending at PD 60. Anxiety, a potential side effect of stimulant treatment, was assessed using three paradigms: The open field test (OF), the social interaction test (SI), and the elevated plus maze (EPM). The OF and SI were conducted using repeated testing over the course of five weeks. Testing occurred immediately after drug administration on a given day. The EPM was used only once on the penultimate day of treatment, before the drug was administered. Following drug treatment on PD 60, brain-to-body weight ratios were obtained. Results indicated that there were no group differences in brain-to-body weight ratios nor were differences in locomotor and social behaviors observed. However, rats treated with DL-amphetamine did show an anxiogenic response in the EPM. This was represented as a significant reduction in open arm entries. Overall our findings suggest that while chronic drug treatment fails to alter multiple measures of behavior, or reliable changes in brain volume, such treatment may impact a behavioral index of anxiety. Future research should seek to examine the implications of this heightened anxiogenic response in animals treated chronically with oral, low-dose DL-amphetamine.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Kafka, A. , Heinz, D. , Flemming, T. and Currie, P. (2014) Effect of Chronic DL-Amphetamine Exposure on Brain Volume, Anxiogenic, Locomotor, and Social Behaviors in Male SD Rats. Journal of Behavioral and Brain Science, 4, 375-383. doi: 10.4236/jbbs.2014.48036.

References

[1] Hodgkins, P., Shaw, M., McCarthy, S. and Sallee, F.R. (2012) The Pharmacology and Clinical Outcomes of Amphetamines to Treat ADHD: Does Composition Matter? CNS Drugs, 26, 245-268.
http://dx.doi.org/10.2165/11599630-000000000-00000
[2] Hisle-Gorman, E., Eide, M., Coll, E.J. and Gorman, G.H. (2014) Attention Deficit Hyperactivity Disorder and Medication Use by Children During Parental Military Deployments. Military Medicine, 179, 573-578.
http://dx.doi.org/10.7205/MILMED-D-13-00334
[3] Wolraich, M.L. (1999) Attention Deficit Hyperactivity Disorder: The Most Studied and Yet the Most Controversial Diagnosis. Mental Retardation and Developmental Disabilities Research Reviews, 5, 163-1688.
[4] American Psychiatric Association (2013) Neurodevelopmental Disorders (5th Edition). The Diagnostic and Statistical Manual of Mental Disorders, 59-66.
http://dx.doi.org/10.1176/appi.books.9780890425596.514988
[5] Polanczyk, G. and Rohde, L.A. (2007) Epidemiology of Attention-Deficit/Hyperactivity Disorder across the Lifespan. Current Opinion in Psychiatry, 20, 386-392.
http://dx.doi.org/10.1097/YCO.0b013e3281568d7a
[6] Faraone, S.V. and Biederman, J. (2005) What Is the Prevalence of Adult ADHD? Results of a Population Screen of 966 Adults. Journal of Attention Disorders, 9, 384-391.
http://dx.doi.org/10.1177/1087054705281478
[7] Visser, S.M., Danielson, M.L., Bitsko, R.H., Holbrook, J.R., Kogan, M.D., Ghandour, R.M., Perou, R. and Blumberg, S.J. (2014) Trends in the Parent Report of Healthcare Provider-Diagnosed and Medicated Attention-Deficit/Hyperactivity Disorder: United States, 2003-2011. Journal of the American Academy of Child and Adolescent Psychiatry, 53, 34-46.
http://dx.doi.org/10.1016/j.jaac.2013.09.001
[8] Rowland, A.S., Umbach, D.M., Catoe, K.E., Stallone, L., Long, S., Rabiner, D., Naftel, A.J., Panke, D., Faulk, R. and Sandler, D.P. (2001) Studying the Epidemiology of Attention-Deficit Hyperactivity Disorder: Screening Method and Pilot Results. Canadian Journal of Psychiatry, 46, 931-940.
[9] Price, J.H., Khubchandani, J., McKinney, M. and Braun, R. (2013) Racial/Ethnic Disparities in Chronic Diseases of Youths and Access to Health Care in the United States. BioMed Research International, 2013, Article ID: 787616.
http://dx.doi.org/10.1155/2013/787616
[10] Zuvekas, S., Vitiello, B. and Norquist, G. (2006) Recent Trends in Stimulant Medication Use Among US Children. The American Journal of Psychiatry, 163, 579-585.
http://dx.doi.org/10.1176/appi.ajp.163.4.579
[11] Fleckenstein, A.E., Volz, T.J., Riddle, E.L., Gibb, J.W. and Hanson, G.R. (2007) New Insights into the Mechanism of Action of Amphetamines. Annual Review of Pharmacology and Toxicology, 47, 681-698.
http://dx.doi.org/10.1146/annurev.pharmtox.47.120505.105140
[12] Aagaard, L. and Hansen, E.H. (2011) The Occurrence of Adverse Drug Reactions Reported for Attention Deficit Hyperactivity Disorder (ADHD) Medications in the Pediatric Population: A Qualitative Review of Empirical Studies. Neuropsychiatric Disease and Treatment, 7, 729-744.
http://dx.doi.org/10.2147/NDT.S26403
[13] Zito, J.M., Safer, D.J., dos Reis, S., Gardner, J.F., Boles, M. and Lynch, F. (2000) Trends in the Prescribing of Psychotropic Medications to Preschoolers. The Journal of the American Medical Association, 283, 1025-1030.
http://dx.doi.org/10.1001/jama.283.8.1025
[14] Andersen, S.L. and Teicher, M.H. (2000) Sex Differences in Dopamine Receptors and Their Relevance to ADHD. Neuroscience & Biobehavioral Reviews, 24, 137-141.
http://dx.doi.org/10.1016/S0149-7634(99)00044-5
[15] Brenhouse, H.C. and Andersen, S.L. (2011) Developmental Trajectories during Adolescence in Males and Females: A Cross-Species Understanding of Underlying Brain Changes. Neuroscience & Biobehavioral Reviews, 35, 1687-1703.
http://dx.doi.org/10.1016/j.neubiorev.2011.04.013
[16] Rakic, P., Bourgeois, J.P., Eckenhoff, M.F., Zecevic, N. and Goldman-Rakic, P.S. (1986) Concurrent Overproduction of Synapses in Diverse Regions of the Primate Cerebral Cortex. Science, 232, 232-235.
http://dx.doi.org/10.1126/science.3952506
[17] Efron, D., Jarman, F. and Barker, M. (1997) Side Effects of Methylphenidate and Dexamphetamine in Children with Attention Deficit Hyperactivity Disorder: A Double-Blind, Crossover Trial. Pediatrics, 100, 662-666.
http://dx.doi.org/10.1542/peds.100.4.662
[18] Pliszka, S.R., Browne, R.G., Olvera, R.L. and Wynne, S.K. (2000) A Double-Blind, Placebo-Controlled Study of Adderall and Methylphenidate in the Treatment of Attention-Deficit/Hyperactivity Disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 39, 619-626.
http://dx.doi.org/10.1097/00004583-200005000-00016
[19] Ahmann, P.A., Theye, F.W., Berg, R., Linquist, A.J., Van Erem, A.J. and Campbell, L.R. (2001) Placebo-Controlled Evaluation of Amphetamine Mixture—Dextroamphetamine Salts and Amphetamine Salts (Adderall): Efficacy Rate and Side Effects. Pediatrics, 107, e10-e10.
http://dx.doi.org/10.1542/peds.107.1.e10
[20] Lakhan, S.E. and Kirchgessner, A. (2012) Prescription Stimulants in Individuals with and without Attention Deficit Hyperactivity Disorder: Misuse, Cognitive Impact, and Adverse Effects. Brain and Behavior, 2, 661-677.
http://dx.doi.org/10.1002/brb3.78
[21] Clausing, P., Gough, B., Holson, R.R., Slikker, W. and Bowyer, J.F. (1995) Amphetamine Levels in Brain Microdialysate, Caudate/Putamen, Substantia Nigra and Plasma after Dosage That Produces Either Behavioral or Neurotoxic Effects. Journal of Pharmacology and Experimental Therapeutics, 274, 614-621.
[22] Kita, T., Asanuma, M., Miyazaki, I. and Takeshima, M. (2014) Protective Effects of Phytochemical Antioxidants against Neurotoxin-Induced Degeneration of Dopaminergic Neurons. Journal of Pharmacological Sciences, 124, 313-319.
http://dx.doi.org/10.1254/jphs.13R19CP
[23] Berman, S.M., Kuczenski, R., McCracken, J.T. and London, E.D. (2008) Potential Adverse Effects of Amphetamine Treatment on Brain and Behavior: A Review. Molecular Psychiatry, 14, 123-142.
http://dx.doi.org/10.1038/mp.2008.90
[24] Ricaurte, G.A., Mechan, A.O., Yuan, J., Hatzidimitriou, G., Xie, T., Mayne, A.H. and McCann, U.D. (2005) Amphetamine Treatment Similar to That Used in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder Damages Dopaminergic Nerve Endings in the Striatum of Adult Non-human Primates. Journal of Pharmacology and Experimental Therapeutics, 315, 91-98.
http://dx.doi.org/10.1124/jpet.105.087916
[25] Andersen, S.L. (2003) Trajectories of Brain Development: Point of Vulnerability or Window of Opportunity? Neuroscience & Biobehavioral Reviews, 27, 3-18.
http://dx.doi.org/10.1016/S0149-7634(03)00005-8
[26] Allen, J.K., Wilkinson, M., Soo, E.C., Hui, J.P.M., Chase, T.D. and Carrey, N. (2010) Chronic Low Dose Adderall XR® Down-Regulates cfos Expression in Infantile and Prepubertal Rat Striatum and Cortex. Neuroscience, 169, 1901-1912.
http://dx.doi.org/10.1016/j.neuroscience.2010.06.029
[27] Chase, T.D., Carrey, N., Soo, E. and Wilkinson, M. (2007) Methylphenidate Regulates Activity Regulated Cytoskeletal Associated but Not Brain-Derived Neurotrophic Factor Gene Expression in the Developing Rat Striatum. Neuroscience, 144, 969-984.
http://dx.doi.org/10.1016/j.neuroscience.2006.10.035
[28] Ramos, A., Homem, K.S.D.C., Suchecki, D., Tufik, S. and Troncone, L.RP. (2014) Drug-Induced Suppression of ACTH Secretion Does Not Promote Anti-Depressive or Anxiolytic Effects. Behavioural Brain Research, 265, 69-75.
http://dx.doi.org/10.1016/j.bbr.2014.02.024
[29] Rainer, Q., Speziali, S., Rubino, T., Dominguez-Lopez, S., Bambico, F.R., Gobbi, G. and Parolaro, D. (2014) Chronic Nandrolone Decanoate Exposure during Adolescence Affects Emotional Behavior and Monoaminergic Neurotransmission in Adulthood. Neuropharmacology, 83, 79-88.
http://dx.doi.org/10.1016/j.neuropharm.2014.03.015
[30] Currie, P.J., Schuette, L.M., Wauson, S.E., Voss, W.N. and Angeles, M.J. (2014) Activation of Urocortin 1 and Ghrelin Signaling in the Basolateral Amygdala Induces Anxiogenesis. NeuroReport, 25, 60-64.
[31] Narine, C., Sarwar, S.R. and Rais, T.B. (2013) Adderall-Induced Trichotil-lomania: A Case Report. Innovations in Clinical Neuroscience, 10, 13.
[32] Melega, W.P., Raleigh, M.J., Stout, D.B., Lacan, G., Huang, S.C. and Phelps, M.E. (1997) Recovery of Striatal Dopamine Function after Acute Amphetamine- and Methamphetamine-Induced Neurotoxicity in the Vervet Monkey. Brain Research, 766, 113-120.
http://dx.doi.org/10.1016/S0006-8993(97)00548-9
[33] Segal, D.S. and Kuczenski, R. (1997) Repeated Binge Exposures to Amphetamine and Methamphetamine: Behavioral and Neurochemical Characterization. Journal of Pharmacology and Experimental Therapeutics, 282, 561-573.
[34] Jedema, H.P., Narendran, R. and Bradberry, C.W. (2014) Amphetamine-Induced Release of Dopamine in Primate Prefrontal Cortex and Striatum: Striking Differences in Magnitude and Timecourse. Journal of Neurochemistry, Early View.
http://dx.doi.org/10.1111/jnc.12743
[35] Ren, J., Xu, H., Choi, J.K., Jenkins, B.G. and Chen, Y. (2009) Dopaminergic Response to Graded Dopamine Concentration Elicited by Four Amphetamine Doses. Synapse, 63, 764-772.
http://dx.doi.org/10.1002/syn.20659
[36] Swanson, J.M., Elliott, G.R., Greenhill, L.L., Wigal, T., Arnold, L.E., Vitiello, B., et al. (2007) Effects of Stimulant Medication on Growth Rates across 3 Years in the MTA Follow-Up. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 1015-1027.
http://dx.doi.org/10.1097/chi.0b013e3180686d7e
[37] Jones, Z., Vazquez, C.R. and Dafny, N. (2014) Ventral Tegmental Area Neuronal Activity Correlates to Animals’ Behavioral Response to Chronic Methylphenidate Recorded from Adolescent SD Male Rats. Journal of Behavioral and Brain Science, 4, 168-189.
http://dx.doi.org/10.4236/jbbs.2014.44020
[38] Cepko, L.C.S., Selva, J.A., Merfeld, E.B., Fimmel, A.I., Goldberg, S.A. and Currie, P.J. (2014) Ghrelin Alters the Stimulatory Effect of Cocaine on Ethanol Intake Following Mesolimbic or Systemic Administration. Neuropharmacology, 85, 224-231.
http://dx.doi.org/10.1016/j.neuropharm.2014.05.030
[39] Schuette, L.M., Gray, C.C. and Currie, P.J. (2013) Microinjection of Ghrelin into the Ventral Tegmental Area Potentiates Cocaine-Induced Conditioned Place Preference. Journal of Behavioral and Brain Science, 3, 576-580.
http://dx.doi.org/10.4236/jbbs.2013.38060

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.