JBBS> Vol.2 No.2, May 2012

Adolescent Exposure of JWH-018 “Spice” Produces Subtle Effects on Learning and Memory Performance in Adulthood

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ABSTRACT

The active components associated with the bio-designer drugs known variously as “Spice” or “K2” have rapidly gained in popularity among recreational users, forcing the United States Drug Enforcement Administration to classify these compounds as Schedule I drugs in the Spring of 2011. However, although there is some information about many of the synthetic cannabinoids used in Spice products, little is known about the consequences of the main constituent, (1-pentyl-3-(1-naphthoyl)indole; JWH-018), on neuropsychological development or behavior. In the present experiment, adolescent rats were given repeated injections of either saline or 100 μg/kg of JWH-018. Once the animals were 75 days of age, they were trained using tasks with spatial components of various levels of difficulty and a spatial learning set task. On early trials with water maze tasks of varying difficulty, the JWH-018 treated rats were impaired relative to controls. However, by the end of each phase of testing, drug and control animals were comparable, although on probe trials the drug-treated animals spent significantly less time in the target quadrant. In addition, the performance of the drug-treated rats was inferior to that of the control animals on a learning set task, suggesting some difficulty in adapting their responses to changing task demands. The results suggest that chronic exposure to this potent cannabinoid CB1 receptor agonist during adolescence is capable of producing a variety of subtle changes affecting spatial learning and memory performance in adulthood, well after the drug exposure period.

Cite this paper

D. Compton, M. Seeds, G. Pottash, B. Gradwohl, C. Welton and R. Davids, "Adolescent Exposure of JWH-018 “Spice” Produces Subtle Effects on Learning and Memory Performance in Adulthood," Journal of Behavioral and Brain Science, Vol. 2 No. 2, 2012, pp. 146-155. doi: 10.4236/jbbs.2012.22017.

References

[1] I. Sví?enská, P. Dubovy and A. ?ulcová, “Cannabinoid Receptors 1 and 2 (CB1 and CB2), Their Distribution, Ligands and Functional Involvement in Nervous System Structures—A Short Review,” Pharmacology, Biochemistry and Behavior, Vol. 90, No. 4, 2008, pp. 501-511.
[2] R. I. Block, R. Farinpour and K. Braverman, “Acute Effects of Marijuana on Cognition: Relationships to Chronic Effects and Smoking Techniques,” Pharmacology, Biochemistry and Behavior, Vol. 43, No. 3, 1992, pp. 907-917. doi:10.1016/0091-3057(92)90424-E
[3] J. M. Court, “Cannabis and Brain Function,” Journal of Paediatrics and Child Health, Vol. 34, No. 1, 1998, pp. 1-5. doi:10.1046/j.1440-1754.1998.00142.x
[4] S. J. Heishman, K. Arasteh and M. L. Stitzer, “Comparative Effects of Alcohol and Marijuana on Mood, Memory, and Performance,” Pharmacology, Biochemistry and Behavior, Vol. 58, No. 1, 1997, pp. 93-101. doi:10.1016/S0091-3057(96)00456-X
[5] T. Pattij, J. Wiskerke and A. N. M. Schoffelmeer, “Cannabinoid Modulation of Executive Functions,” European Journal of Pharmacology, Vol. 585, No. 2-3, 2008, pp. 458-463. doi:10.1016/j.ejphar.2008.02.099
[6] G. Riedel and S. N. Davies, “Cannabinoid Function in Learning, Memory and Plasticity,” In: R. G. Pertwee, Ed., Handbook of Experimental Pharmacology, Springer-Verlag, Berlin, 2005, pp. 445-478.
[7] R. G. Pertwee, “The Central Pharmacology of Psychotropic Cannabinoids,” Pharmacological Therapeutics, Vol. 36, No. 2-3, 1988, pp. 189-261. doi:10.1016/0163-7258(88)90106-4
[8] J. S. Myer and L. F. Quenzer, “Psychopharmacology: Drugs, Brain, and Behavior,” Sinauer, Sunderland, 2005.
[9] M. N. Hill and B. B. Gorzalka, “Enhancement of Anxiety-Like Responsiveness to the Cannabinoid CB1 Receptor Agonist HU-210 Following Chronic Stress,” European Journal of Pharmacology, Vol. 499, No. 3, 2004, pp. 291-295. doi:10.1016/j.ejphar.2004.06.069
[10] H. V. Curran, C. Brignell, S. Fletcher, P. Middleton and J. Henry, “Cognitive and Subjective Low-Dose Effects of Acute Oral Δ9Tetrahydrocannabionol (THC) in Infrequent Cannabis Users,” Psychopharmacology, Vol. 164, No. 1, 2002, pp. 61-70. doi:0.1007/s00213-002-1169-0
[11] A. H. Lichtman, S. A. Varvel and B. R. Martin, “Endocannabinoids in Cognition and Dependence,” Prostaglandins, Leukotrienes and Essential Fatty Acids, Vol. 66, No. 2-3, 2002, pp. 269-285. doi:10.1054/plef.2001.0351
[12] N. Solowij, “Cannabis and Cognitive Functioning,” Cambridge University Press, Cambridge, 1998.
[13] H. R. Quinn, I. Matsumoto, P. D. Callaghan, L. E. Long, J. C. Arnold, N. Gunasekaran, M. R. Thompson, B. Dawson, P. E. Mallet, M. A. Kashem, H. Matsuda-Matsumoto, T. Iwazaki and I. S. McGregor, “Adolescent Rats Find Repeated Delta(9)-THC Less Aversive than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure,” Neuropsychopharmacology, Vol. 33, No. 5, 2007, pp. 1113-1126. doi:10.1038/sj.npp.1301475
[14] M. Schneider and M. Koch, “Chronic Pubertal, but Not Adult Chronic Cannabinoid Treatment Impairs Sensorimotor Gating, Recognition Memory and the Performance in a Progressive Ratio Task in Adult Rats,” Neuropsychopharmacology, Vol. 28, No. 10, 2003, pp. 1760-1769. doi:10.1038/sj.npp.1300225
[15] M. O’Shea, M. E. Sing, I. S. McGregor and P. E. Mallet, “Chronic Cannabinoid Exposure Produces Lasting Memory Impairment and Increased Anxiety in Adolescent but Not Adult Rats,” Journal of Psychopharmacology, Vol. 18, No. 4, 2004, pp. 502-508. doi:10.1177/0269881104047277
[16] J. DuBach, “The Allure of ‘Spice’ Officials Claim Herb Mix Is a Dangerous Drug,” Elko Daily Free Press, 2010. http://elkodaily.com/news/local/article_36fca382-cfc8-11df-a3a9-001cc4c002e0.html#ixzz1ZltDQzbJ
[17] I. Vardakou, C. Pistos and C. Spiliopoulou, “Spice Drugs as a New Trend: Mode of Action, Identification and Leg-islation,” Toxicology Letters, Vol. 197, No. 3, 2010, pp. 157-162. doi:10.1016/j.toxlet.2010.06.002
[18] EMCDDA, “Thematic Papers: Understanding the ‘Spice’ Phenomenon,” Lisbon, European Monitoring Centre for Drugs and Drug Addiction, 2009. http://www.emcdda.europa.eu/html.cfm/index90917EN.html
[19] C. Mustata, M. Torrens, R. Pardo, C. Pérez, Psychonaut Web Mapping Group and M. Farré, “Spice Drugs: Cannabinoids as New Designer Drugs [Spanish],” Adicciones, Vol. 21, No. 3, 2009, pp. 181-186.
[20] Psychonaut Web Mapping Research Group, “Psyhonaut Web Mapping Project: Final Report,” Institute of Psychiatry, King’s College London, London, 2010.
[21] United States Drug Enforcement Administration, Office of Forensic Sciences, “Microgram Bulletin,” Vol. 44, No. 3, 2011. http://www.justice.gov/dea/programs/forensicsci/microgram/mg2011/mg0311.pdf
[22] R. Lindigkeit, A. Boehme, I. Eiserloh, M. Luebbecke, M. Wiggermann, L. Ernst and T. Beuerle, “Spice: A Never Ending Story?” Forensic Science International, Vol. 191, No. 1-3, 2009, pp. 58-63. doi:10.1016/j.forsciint.2009.06.008
[23] A. B. Schneir, J. Cullen and B. T. Ly, ‘‘‘Spice’ Girls: Synthetic Cannabinoid Intoxication,” The Journal of Emergency Medicine, Vol. 40, No. 3, 2011, pp. 296-299. doi:10.1016/j.jemermed.2010.10.014
[24] U. S. Zimmermann, P. R. Winkelmann, M. Pilhatsch, J. A. Nees, R. Spanagel and K. Schulz, “Withdrawal Phenomena and Dependence Syndrome after the Consumption of ‘Spice Gold’,” Deutsches ?rzteblatt International, Vol. 106, No. 27, 2009, pp. 464-467. doi:10.3238/arztebl.2009.0464
[25] J. W. Huffman, “Cannabimimetic Indoles, Pyrroles, and Indenes: Structure-Activity Relationships and Receptor Interactions,” In: P. H. Reggio, Ed., The Cannabinoid Receptors, Human Press, New York, 2009, pp. 49-94. doi:10.1007/978-1-59745-503-9_3
[26] J. L. Wiley, D. R. Compton, D. Dai, J. A. H. Lainton, M. Phillips, J. W. Huffman and B. R. Martin, “Structure-Activity Relationships of Indole- and Pyrrole-Derived Cannabinoids,” Journal of Pharmacology and Experimental Therapeutics, Vol. 285, No. 3, 1998, pp. 995-1004.
[27] AAPCC, “Fake Marijuana Spurs More than 2500 Calls to US Poison Centers This Year Alone,” American Association of Poison Control Centers, Alexandria, 2010.
[28] EMCDDA, “Annual Report on the State of the Drugs Problem,” European Monitoring Centre for Drugs and Drug Addiction, Lisbon, 2009.
[29] C. G. Lyketsos, E. Garrett, K. Y. Liang and J. C. Anthony, “Cannabis Use and Cognitive Decline in Persons under 65 Years of Age,” American Journal of Epidemiology, Vol. 149, No. 9, 1999, pp. 794-800. doi:10.1093/oxfordjournals.aje.a009894
[30] P. Fried, B. Watkinson, D. James and R. Gray, “Current and Former Marijuana Use: Preliminary Findings of a Longitudinal Study of Effects on 10 in Young Adults,” Journal of the Canadian Medical Association, Vol. 166, No. 7, 2002, pp. 887-891.
[31] A. Stiglick and H. Kalant, “Residual Effects of Chronic Cannabis Treatment on Behavior in Mature Rats,” Psy- chopharmacology, Vol. 85, No. 4, 1985, pp. 436-439. doi:10.1007/BF00429660
[32] M. Schneider, E, Drews and M. Koch, “Behavioral Ef- fects in Adult Rats of Chronic Prepubertal Treatment with the Cannabinoid Receptor Agonist WIN 55212-2,” Be- havioural Pharmacology, Vol. 16, No. 5-6, 2005, pp. 447-453. doi:10.1097/00008877-200509000-00018
[33] M. Schneider, E. Sch?mig and F. M. Leweke, “Acute and Chronic Cannabinoid Treatment Differentially Affects Recognition Memory and Social Behavior in Pubertal and Adult Rats,” Addiction Biology, Vol. 13, No. 3-4, 2008, pp. 345-357. doi:10.1111/j.1369-1600.2008.00117.x
[34] D. Giuliani, F. Ferrari and A. Ottani, “The Cannabinoid Agonist HU 210 Modifies Rat Behavioural Responses to Novelty and Stress,” Pharmacological Research, Vol. 41, No. 1, 2000, pp. 45-51. doi:10.1006/phrs.1999.0560
[35] M. Biscaia, S. Mar?in, B. Ferna?ndez, E. M. Marco, M. Rubio, C. Guaza, E. Ambrosio and M. P. Viveros, “Chronic Treatment with CP 55,940 during the Peri- Adolescent Period Differentially Affects the Behavioural Responses of Male and Female Rats in Adulthood,” Psy- chopharmacology, Vol. 170, No. 3, 2003, pp. 301-308. doi:10.1007/s00213-003-1550-7
[36] E. Tirelli, G. Laviola and W. Adriani, “Ontogenesis of Behavioral Sensitization and Conditioned Place Prefer- ence in Laboratory Rodents,” Neuroscience and Biobe- havioral Reviews, Vol. 27, No. 1-2, 2003, pp. 163-178. doi:10.1016/S0149-7634(03)00018-6
[37] L. P. Spear, “The Adolescent Brain and Age-Related Behavioral Manifestations,” Neuroscience and Biobe- havioral Reviews, Vol. 24, No. 4, 2000, pp. 417-463. doi:10.1016/S0149-7634(00)00014-2
[38] Psychonaut Web Mapping Research Group, “Spice Re- port,” Institute of Psychiatry, King’s College London, Lon- don, 2009.
[39] S. Every-Palmer, “Synthetic Cannabinoid JWH-018 and Psychosis: An Explorative Study,” Drug and Alcohol Dependence, Vol. 117, No. 2-3, pp. 152-157. doi:10.1016/j.drugalcdep.2011.01.012
[40] Kikura-Hanajiri, N. Uchiyama and Y. Goda, “Survey of Current Trends in the Abuse of Psychotropic Substances and Plants in Japan,” Legal Medicine, Vol. 13, No., 3, 2011, pp. 109-115. doi:10.1016/j.legalmed.2011.02.003
[41] L. W. Padgett, “Recent Developments in Cannabinoid Ligands,” Life Sciences, Vol. 77, No. 14, 2005, pp. 1767- 1798. doi:10.1016/j.lfs.2005.05.020
[42] M. M., Schmidt, A. Sharma, F. Schifano and C. Fein- mann, “‘Legal Highs’ on the Net: Evaluation of UK- Based Websites, Products and Product Information,” Fo- rensic Science International, Vol. 206, No. 1-3, 2011, pp. 92-97. doi:10.1016/j.forsciint.2010.06.030
[43] T. Sobolevsky, I. Prasolow and G. Rodchenkow, “Detection of JWH-018 Metabolites in Smoking Mixture Post- Administration Urine,” Forensic Science International, Vol. 200, No. 1-3, 2010, pp. 141-147. doi:10.1016/j.forsciint.2010.04.003
[44] Institute of Laboratory Animal Research, Commission on Life Sciences, “Guide for the Care and Use of Laboratory Animals,” National Academies Press, Washington, 1996.
[45] R. P. Kesner, B. V. DiMattia and K. A. Crutcher, “Evi- dence for Neocortical Involvement in Reference Mem- ory,” Behavioral and Neural Biology, Vol. 47, No. 1, 1987, pp. 40-53. doi:10.1016/S0163-1047(87)90145-2
[46] A. K?falvi, Ed., “Cannabinoids and the Brain,” Springer, New York, 2008.
[47] R. G. Pertwee, “Pharmacological Actions of Cannabi- noids,” In: R. G. Pertwee, Ed., Cannabinoids: Handbook of Experimental Pharmacology (Vol. 168), Springer- Verlag, Heidelberg, 2005, pp. 1-52.
[48] A. Ameri, “The effects of Cannabinoids on the Brain,” Progress in Neurobiology, Vol. 58, No. 4, 1999, pp. 315- 348. doi:10.1016/S0301-0082(98)00087-2
[49] C. S. Kearn and C. J. Hilliard, “Rat Microglial Cell Express the Peripheral-Type Cannabinoid Receptor (CB2) Which Is Negatively Coupled to Adenylyl Cyclase,” In- ternational Cannabinoid Research Society, Vol. 1, Sym- posium on Cannabinoids, Burlington, p. 61.
[50] J. P. Gong, E. S. Onaivi, H. Ishiguro, Q. R. Liu, P. A. Tagliaferro, A. Brusco, and G. R. Uhl, “Cannabinoid CB2 receptors: Immunohistochemical Localization in Rat Brain,” Brain Research, Vol. 1071, No. 1, 2006, pp. 10-23. doi:10.1016/j.brainres.2005.11.035
[51] N. Hajos and T. F. Freund, “Pharmacological Separation of Cannabinoid Sensitive Receptors on Hippocampal Ex- citatory and Inhibitory Fibers,” Neuropharmacology, Vol. 43, No. 4, 2002, pp. 503-510. doi:10.1016/S0028-3908(02)00157-0
[52] M. Herkenham, A. B. Lynn, M. D. Little, M. R. Johnson, L. S. Melvin, B. R. de Costa and K. C. Rice, “Cannabi- noid Receptor Localization in Brain,” Proceedings of Na- tional Academy of Science USA, Vol. 87, No. 5, 1990, pp. 1932-1936.
[53] I. Katona, E. A. Rancz, L. Acsady, C. Ledent, K. Mackie, N. Hajos and T. F. Freund, “Distribution of CB1 Cannabinoid Receptors in the Amygdala and Their Role in the Control of GABAergic Transmission,” The Journal of Neuroscience, Vol. 21, No. 23, 2001, pp. 9506-9518.
[54] S. J. Carlisle, F. Marciano-Cabral, A. Staab, C. Ludwick, and G. A. Cabral, “Differential Expression of the CB2 Cannabinoid Receptor by Rodent Macrophages and Macro- phage-Like Cells in Relation to Cell Activation,” Interna- tional Immunopharmacology, Vol. 2, No. 1, 2002, pp. 69-82. doi:10.1016/S1567-5769(01)00147-3
[55] J. M. Sullivan, “Cellular and Molecular Mechanisms Underlying Learning and Memory Impairments Produced by Cannabinoids,” Learning and Memory, Vol. 7, No. 3, 2000, pp. 132-139. doi:10.1101/lm.7.3.132
[56] S. N. Davies, R. G. Pertwee and G. Riedel, “Functions of Cannabinoid Receptors in the Hippocampus,” Neuro- pharmacology, Vol. 42, No. 8, 2002, pp. 993-1007. doi:10.1016/S0028-3908(02)00060-6
[57] S. Da and R. N. Takahashi, “SR 141716A Prevents Delta 9-Tetrahydrocannabinol Induced Spatial Learning Deficit in a Morris-Type Water Maze in Mice,” Progress in Neu- ropsychopharmacology and Biological Psychiatry, Vol. 26, No. 2, 2002, pp. 321-325. doi:10.1016/S0278-5846(01)00275-5
[58] L. Robinson, A. V. Goonawardena, R. G. Pertwee, R. E. Hampson and G. Riedel, “The Synthetic Cannabinoid HU210 Induces Spatial Memory Deficits and Suppresses Hippocampal Firing Rate in Rats,” British Journal of Pharmacolology, Vol. 151, No. 5, 2007, pp. 688-700. doi:10.1038/sj.bjp.0707273
[59] S. A. Varvel, E. Anum, F. Niyuhire, L. E. Wise and A. H. Lichtman, “Delta(9)-THC-Induced Cognitive Deficits in Mice Are Reversed by the GABA(A) Antagonist Bicuculline,” Psychopharmacology, Vol. 178, No. 2-3, 2005, pp. 317-327. doi:10.1007/s00213-004-1988-2
[60] S. A. Varvel, R. J. Hamm, B. R. Martin and A. H. Licht- man, “Differential Effects of Delta 9-THC on Spatial Ref- erence and Working Memory in Mice,” Psychopharma- cology, Vol. 157, No. 2, 2001, pp. 142-150. doi:10.1007/s002130100780
[61] K. Mishima, N. Egashira, N. Hirosawa, M. Fujii, Y. Ma- tsumoto, K. Iwasaki and M. Fujiwara, “Characteristics of Learning and Memory Impairment Induced by Delta9- tetrahydrocannabinol in Rats,” The Japanese Journal of Pharmacology, Vol. 87, No. 4, 2001, pp. 297-308. doi:10.1254/jjp.87.297
[62] E. M. Nakamura, E. A. da Silva, G. V. Concilio, D. A. Wilkinson and J. Masur, “Reversible Effects of Acute and Long-Term Administration of Delta-9-Tetrahydrocan- nabinol (THC) on Memory in the Rat,” Drug and Alcohol Dependence, Vol. 28, No. 2, 1991, pp. 167-175. doi:10.1016/0376-8716(91)90072-7
[63] N. Wegener, S. Kuhnert, A. Thuns, R. Roese and M. Koch, “Effects of Acute Systemic and Intra-Cerebral Stimu- lation of Cannabinoid Receptors on Sensorimotor Gating, Locomotion And Spatial Memory in Rats,” Psychophar- macology, Vol. 198, No. 3, 2008, pp. 375-385. doi:10.1007/s00213-008-1148-1
[64] L. E. Wise, A. J. Thorpe and A. H. Lichtman, “Hippo- campal CB(1) Receptors Mediate the Memory Impairing Effects of Delta(9)-Tetrahydrocannabinol,” Neuropsycho- pharmacology, Vol. 34, No. 9, 2009, pp. 2072-2080. doi:10.1038/npp.2009.31
[65] T. T. Yim, N. S. Hong, M. Ejaredar, J. E. McKenna and R. J. McDonald, “Post-Training CB1 Cannabinoid Re- ceptor Agonist Activation Disrupts Long-Term Consoli- dation of Spatial Memories in the Hippocampus,” Neuro- science, Vol. 151, No. 4, 2008, pp. 929-936. doi:10.1016/j.neuroscience.2007.08.037
[66] S. K. Acheson, N. L. T. Moore, C. M. Kuhn, W. A. Wil- son and H. S. Swartzwelder, “The Synthetic Cannabinoid WIN 55212-2 Differentially Modulates Thigmotaxis but Not Spatial Learning in Adolescent And Adult Animals,” Neuroscience Letters, Vol. 487, No. 3, 2011, pp. 411-414. doi:10.1016/j.neulet.2010.10.067
[67] I. Akirav, “The Role of Cannabinoids in Modulating Emo- tional and Nonemotional Memory Processes in the Hip- pocampus,” Frontiers in Behavioral Neuroscience, Vol. 5, 2011, p. 34. http://www.frontiersin.org/behavioral_neuroscience/10.3389/fnbeh.2011.00034/full
[68] D. L. Misner and J. M. Sullivan, “Mechanism of Can- nabinoid Effects on Long Term Potentiation and Depres- sion in Hippocampal CA1 Neurons,” Journal of Neuro- science, Vol. 19, No. 16, 1999, pp. 6795-6805.
[69] M. Shen, T. M. Piser, V. S. Seybold and S. A. Thayer, “Cannabinoid Receptor Agonists Inhibit Glutamatergic Synaptic Transmission in Rat Hippocampal Cultures,” The Journal of Neuroscience, Vol. 16, No. 14, 1996, pp. 4322-4334.
[70] A. V. Nowicky, T. J. Teyler and R. M. Vardaris, “The Modulation of Long Term Potentiation by Delta-9-Tet- rahydrocannabinol in the Rat Hippocampus, in Vitro,” Brain Research Bulletin, Vol. 19, No. 6, 1987, pp. 663- 672. doi:10.1016/0361-9230(87)90052-9
[71] D. R. Collins, R. G. Pertwee and S. N. Davies, “The Ac- tion of Synthetic Cannabinoids on the Induction of Long- Term Potentiation in the Rat Hippocampal Slice,” Euro- pean Journal of Pharmacology, Vol. 259, No. 3, 1994, pp. R7-R8. doi:10.1016/0014-2999(94)90666-1
[72] D. R. Collins, R. G. Pertwee and S. N. Davies, “Preven- tion by the Cannabinoid Antagonist, SR141716A, of Can- nabinoid-Mediated Blockade of Long-Term Potentiation in the Rat Hippocampal Slice,” British Journal of Phar- macology, Vol. 115, No. 6, 1995, pp. 869-870.
[73] J. P. Terranova, J. C. Michaud, G. Le Fur and P. Soubrie?, “Inhibition of Long-Term Potentiation in Rat Hippocam- pal Slices by Anandamide and WIN55212-2: Reversal by SR141716 A, a Selective Antagonist of CB1 Cannabinoid Receptors,” Naunyn-Schmiedeberg’s Archives of Phar- macology, Vol. 352, No. 5, 1995, pp. 576-579. doi:10.1007/BF00169393
[74] W. Adriani and G. Laviola, “Windows of Vulnerability to Psychopathology and Therapeutic Strategy in the Ado- lescent Rodent Model,” Behavioural Pharmacology, Vol. 15, No. 5-6, 2004, pp. 341-352. doi:10.1097/00008877-200409000-00005
[75] M. R. Domenici, S. C. Azad, G. Marsicano, A. Schierloh, C. T. Wotjak, H. U. Dodt, W. Zieglgansberger, B. Lutz and G. Rammes, “Cannabinoid Receptor Type 1 Located on Presynaptic Terminals of Principal Neurons in the Forebrain Controls Glutamatergic Synaptic Transmission,” The Journal of Neuroscience, Vol. 26, No. 21, 2006, pp. 5794-5799. doi:10.1523/jneurosci.0372-06.2006
[76] M. Haring, G. Marsicano, B. Lutz and K. Monory, “Iden- tification of the Cannabinoid Receptor Type 1 in Sero- tonergic Cells of Raphe Nuclei in Mice,” Neuroscience, Vol. 146, No. 3, 2007, pp. 1212-1219. doi:10.1016/j.neuroscience.2007.02.021
[77] A. F. Hoffman and C. R. Lupica, “Mechanisms of Can- nabinoid Inhibition of GABA(A) Synaptic Transmission in the Hippocampus,” The Journal of Neuroscience, Vol. 20, No. 7, 2000, pp. 2470-2479.
[78] K. A. Seely, P. L. Prather, L. P. James and J. H. Moran, “Marijuana-Based Drugs: Innovative Therapeutics or De- signer Drugs of Abuse?” Molecular Interventions, Vol. 11, No. 1, 2011, pp. 36-51. doi:10.1124/mi.11.1.6
[79] V. C. Oropeza, K. Mackie and E. J. Van Bockstaele, “Cannabinoid Receptors Are Localized to Noradrenergic Axon Terminals in the Rat Frontal Cortex,” Brain Re- search, Vol. 1127, No. 1, pp. 36-44. doi:10.1016/j.brainres.2006.09.110

  
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