Buspirone Ameliorates the Morphine Withdrawal-Induced Anxiety through Synaptic Ultrastructural Changes in Hippocampus of Rat

Jialin Gao, Gang Qian, Suyuan Luo, Yan Tian, Mingsong Wu, Zhongxiang Yao

1Department of Cell Biology and Genetics, Zunyi Medical College, Zunyi, China 2Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, China.
Department of Cell Biology and Genetics, Zunyi Medical College, Zunyi, China.
Department of Physiology, The Third Military Medical University, Chongqing, China.

DOI: 10.4236/psych.2013.410A003                

Abstract

Morphine administration causes long-lasting neural changes in the brain that underpin the behavioral abnormalities, and the relationship between structural changes and behavioral symptoms is obscure. In present study, the elevated plus-maze and transmission electron microscope were applied to validate the anxiety-like behaviors and synaptic ultrastructural changes in the hippocampi of rats among the morphine group (morphine administration only), the buspirone group (morphine plus buspirone administration) and the vehicle (saline treated only). As compared with the vehicle group, lower values of OE (times of entering into the open arms), OE% (percentage of entries into the open arms), OT (time spent in the open arms), OT% (percentage of time stayed in the open arms), Ns (surface density (Sv)/numerical density (Nv)) and S (surface area) of synapses were observed in the morphine group , but significantly, behavior higher scores of RR (rearing), HD (head-dipping), FBA (flat back approach), and higher Nv, Sv, PSD (postsynaptic density), LPT (length of postsynaptic thickening), WCJ (widths in synaptic cleft on junctions) and CCR (curvature of the cleft region) of synapses appeared in the morphine group. However, no significant differences in values of most of those parameters above were detected between the vehicle group and the buspirone group. These results supported that anxiety-like symptoms of rats significantly occurred to the rats after acute morphine withdrawal, but buspirone administration could reverse these indexes. It also proved that the appearance/disappearance of anxiety-related symptoms was related to the ultrastructural changes/reversibility of synapses in the hippocampus with morphine and buspirone administrations. So, it suggested that anxiety-related symptoms were modified in rats subjected to the synaptic ultrastructural changes in hippocampus by morphine acute withdrawal and were further rehabilitated by buspirone administration. It is helpful to pursue the effective therapeutic methods of morphine addiction.

Keywords

Buspirone; Morphine; Anxiety; Synaptic Ultrastructure; Hippocampus

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Anseloni, V. C., Coimbra, N. C., Morato, S., & Brandao, M. L. (1999). A comparative study of the effects of morphine in the dorsal periaqueductal gray and nucleus accumbens of rats submitted to the elevated plus-maze test. Experimental brain research Experimentelle Hirnforschung, 129, 260-268. http://dx.doi.org/10.1007/s002210050896
[2]	Bals-Kubik, R., Herz, A., & Shippenberg, T. S. (1989). Evidence that the aversive effects of opioid antagonists and kappa-agonists are centrally mediated. Psychopharmacology, 98, 203-206. http://dx.doi.org/10.1007/BF00444692
[3]	Black, J. E., Isaacs, K. R., Anderson, B. J., Alcantara, A. A., & Greenough, W. T. (1990). Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proceedings of the National Academy of Sciences of the United States of America, 87, 5568-5572. http://dx.doi.org/10.1073/pnas.87.14.5568
[4]	Brown, S. M., Napper, R. M., Thompson, C. M., & Mercer, A. R. (2002). Stereological analysis reveals striking differences in the structural plasticity of two readily identifiable glomeruli in the antennal lobes of the adult worker honeybee. Journal of Neuroscience, 22, 8514-8522.
[5]	Devoogd, T. J., Nixdorf, B., & Nottebohm, F. (1985). Synaptogenesis and changes in synaptic morphology related to acquisition of a new behavior. Brain Research, 329, 304-308. http://dx.doi.org/10.1016/0006-8993(85)90539-6
[6]	Dyson, S. E., & Jones, D. G. (1980). Quantitation of terminal parameters and their inter-relationships in maturing central synapses: A perspective for experimental studies. Brain Research, 183, 43-59. http://dx.doi.org/10.1016/0006-8993(80)90118-3
[7]	Ebert, B., Thorkildsen, C., Andersen, S., Christrup, L. L., & Hjeds, H. (1998). Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists. Biochemical Pharmacology, 56, 553-559. http://dx.doi.org/10.1016/S0006-2952(98)00088-4
[8]	Ettenberg, A., & Bernardi, R. E. (2007). Effects of buspirone on the immediate positive and delayed negative properties of intravenous cocaine as measured in the conditioned place preference test. Pharmacology, Biochemistry, and Behavior, 87, 171-178. http://dx.doi.org/10.1016/j.pbb.2007.04.014
[9]	Goto, Y., & Grace, A. A. (2005). Dopamine-dependent interactions between limbic and prefrontal cortical plasticity in the nucleus accumbens: Disruption by cocaine sensitization. Neuron, 47, 255-266. http://dx.doi.org/10.1016/j.neuron.2005.06.017
[10]	Guldner, F. H., & Ingham, C. A. (1980). Increase in postsynaptic density material in optic target neurons of the rat suprachiasmatic nucleus after bilateral enucleation. Neuroscience Letters, 17, 27-31. http://dx.doi.org/10.1016/0304-3940(80)90056-7
[11]	Harris, K. M., & Sultan, P. (1995).Variation in the number, location and size of synaptic vesicles provides an anatomical basis for the nonuniform probability of release at hippocampal CA1 synapses. Neuropharmacology, 34, 1387-1395. http://dx.doi.org/10.1016/0028-3908(95)00142-S
[12]	Jensen, F. E., & Harris, K. M. (1989). Preservation of neuronal ultrastructure in hippocampal slices using rapid microwave-enhanced fixation. Journal of Neuroscience Methods, 29, 217-230. http://dx.doi.org/10.1016/0165-0270(89)90146-5
[13]	Jones, D. G., & Devon, R. M. (1978). An ultrastructural study into the effects of pentobarbitone on synaptic organization. Brain Research, 147, 47-63. http://dx.doi.org/10.1016/0006-8993(78)90771-0
[14]	Klintsova, A. Y., Goodlett, C. R., & Greenough, W. T. (2000). Therapeutic motor training ameliorates cerebellar effects of postnatal binge alcohol. Neurotoxicology and Teratology, 22, 125-132. http://dx.doi.org/10.1016/S0892-0362(99)00052-5
[15]	Koob, G. F. (1992). Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends in Pharmacological Sciences, 13, 177-184. http://dx.doi.org/10.1016/0165-6147(92)90060-J
[16]	Mauk, M. D., Peroutka, S. J., & Kocsis, J. D. (1988). Buspirone attenuates synaptic activation of hippocampal pyramidal cells. Journal of Neuroscience, 8, 1-11.
[17]	Morinville, A., Cahill, C. M., Esdaile, M. J., Aibak, H., Collier, B., Kieffer, B. L., & Beaudet, A. (2003). Regulation of δ-opioid receptor trafficking via μ-opioid receptor stimulation: Evidence from μ-opioid receptor knock-out mice. Journal of Neuroscience, 23, 4888-4898.
[18]	Moron, J. A., Abul-Husn, N. S., Rozenfeld, R., Dolios, G., Wang, R., & Devi, L. A. (2007). Morphine administration alters the profile of hippocampal postsynaptic density-associated proteins: A proteomics study focusing on endocytic proteins. Molecular & Cellular Proteomics, 6, 29-42. http://dx.doi.org/10.1074/mcp.M600184-MCP200
[19]	Morris, R. G., Moser, E. I., Riedel, G. Martin, S. J., Sandin, J., Day, M., & O'Carroll, C. (2003). Elements of a neurobiological theory of the hippocampus: The role of activity-dependent synaptic plasticity in memory. Philosophical Transactions of the Royal Society of London, 358, 773-786. http://dx.doi.org/10.1098/rstb.2002.1264
[20]	Mucha, R. F., & Herz, A. (1985). Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacology, 86, 274-280. http://dx.doi.org/10.1007/BF00432213
[21]	Riblet, L. A., Eison, A. S., Eison, M. S., Taylor, D. P., Temple, D. L., & VanderMaelen, C. P. (1986). Neuropharmacology of buspirone. Psychopathology, 17, 69-78. http://dx.doi.org/10.1159/000284133
[22]	Safiulina, V. F., Kas'yanov, A. M., Markevich, V. A., Bogdanova, O. G., Dvorzhak, A. Y., Zosimovskii, V. A., & Ezrokhi, V. L. (2005). Studies of the synaptic plasticity of field CA3 of the hippocampus during tetanization of the perforant path. Neuroscience and Behavioral Physiology, 35, 693-698. http://dx.doi.org/10.1007/s11055-005-0112-3
[23]	Salmanzadeh, F., Fathollahi, Y., Semnanian, S., Shafizadeh, M., & Kazemnejad, A. (2003). Dependence on morphine leads to a prominent sharing among the different mechanisms of long-term potentiation in the CA1 region of rat hippocampus. Brain research, 963, 93-100. http://dx.doi.org/10.1016/S0006-8993(02)03947-1
[24]	Scheuermann, D. W., Krammer, H. J., Timmermans, J. P., Stach, W., Adriaensen, D., & De Groodt-Lasseel, M. H. (1991). Fine structure of morphologically well-defined type II neurons in the enteric nervous system of the porcine small intestine revealed by immunoreactivity for calcitonin gene-related peptide. Acta Anatomica, 142, 236-241. http://dx.doi.org/10.1159/000147195
[25]	Shakesby, A. C., Anwyl, R., & Rowan, M. J. (2002). Overcoming the effects of stress on synaptic plasticity in the intact hippocampus: rapid actions of serotonergic and antidepressant agents. Journal of Neuroscience, 22, 3638-3644.
[26]	Shepherd, G. M., & Harris, K. M. (1998). Three-dimensional structure and composition of CA3-->CA1 axons in rat hippocampal slices: Implications for presynaptic connectivity and compartmentalization. Journal of Neuroscience, 18, 8300-8310.
[27]	Sterio, D. C. (1984). The unbiased estimation of number and sizes of arbitrary particles using the disector. Journal of Microscopy, 134, 127-136. http://dx.doi.org/10.1111/j.1365-2818.1984.tb02501.x
[28]	Swift, R. M., & Stout, R. L. (1992). The relationship between craving, anxiety, and other symptoms in opioid withdrawal. Journal of Substance Abuse, 4, 19-26. http://dx.doi.org/10.1016/0899-3289(92)90024-R
[29]	Turner, A. M., & Greenough, W. T. (1985). Differential rearing effects on rat visual cortex synapses. I. Synaptic and neuronal density and synapses per neuron. Brain Research, 329, 195-203. http://dx.doi.org/10.1016/0006-8993(85)90525-6
[30]	Trulson, M. E., & Arasteh, K. (1986). Buspirone decreases the activity of 5-hydroxytryptamine-containing dorsal raphe neurons in-vitro. The Journal of Pharmacy and Pharmacology, 38, 380-382. http://dx.doi.org/10.1111/j.2042-7158.1986.tb04591.x
[31]	Weibel, E. R., Kistler, G. S., & Scherle, W. F. (1966). Practical stereological methods for morphometric cytology. The Journal of Cell Biology, 30, 23-38. http://dx.doi.org/10.1083/jcb.30.1.23
[32]	Withers, G. S., Fahrbach, S. E., & Robinson, S. E. (1993). Selective neuroanatomical plasticity and division of labour in the honeybee. Nature, 364, 238-240. http://dx.doi.org/10.1038/364238a0
[33]	Yocca, F. D. (1990). Neurochemistry and neurophysiology of buspirone and gepirone: Interactions at presynaptic and postsynaptic 5HT1A receptors. Journal of clinical psychopharmacology, 10, 6S-12S. http://dx.doi.org/10.1097/00004714-199006001-00003
[34]	Yuan, X. R., Madamba, S., & Siggins, G. R. (1992). Opioid peptides reduce synaptic transmission in the nucleus accumbens. Neuroscience Letters, 134, 223-228. http://dx.doi.org/10.1016/0304-3940(92)90522-9
[35]	Zhang, Z., & Schulteis, G. (2008). Withdrawal from acute morphine dependence is accompanied by increased anxiety-like behavior in the elevated plus maze. Pharmacology, Biochemistry, and Behavior, 89, 392-403. http://dx.doi.org/10.1016/j.pbb.2008.01.013