Tevfik ALICI, Tayfun İ. UZBAY

2643

Kannabinoidler: Ödüllendirici ve bağımlılık yapıcı etkilerinin nörobiyolojisi ve nöropsikofarmakolojisi üzerine bir gözden geçirme

Kannabinoidler ağrıyı gidermek ve bulantı-kusmayı önlemek gibi terapötik yararı olan etkilerin yanı sıra bağımlılığa yol açmak gibi olumsuz etkilere de sahiptir. Esrar, günümüzde en yaygın kötüye kullanılan yasadışı madde olmakla birlikte, bu bitkinin temel psikoaktif maddesi olan A9--Tetrahidrokannabinolün ödüllendirici etkisi ve bununla doğrudan ilişkili olan bağımlılık oluşturucu etkisinin araştırılmasında deneysel modellerin kullanımı daha yakın tarihlere dayanmaktadır. Özgül kanabinoid reseptörlerinin ve bu reseptörlere bağlanan endojen ligandların keşfinden sonra ve seçici kannabinoid CB1 reseptör antagonisti SR141716A ve transgenik modellerin sağladığı olanaklarla son yirmi yılda kanabinoidlerin ödüllendirici ve bağımlılık yapıcı etkilerinin altında yatan nöronal etki düzenekleri konusunda hızlı bir ilerleme kaydedilmiştir. Bu derleme makalede, ilaç diskriminasyon yöntemi, koşullu yer tercihi, kendine-uygulama ve antagonistic presipite edilmiş yoksunluk sendromu gibi hayvan modelleri kullanılarak kannabinoidlerin ödüllendirici ve bağımlılık yapıcı etkileri ve bu etkilerin altında yatan nöronal etki düzenekleri konusunda yapılan çalışmaların olabildiğince kapsamlı bir taraması ve değerlendirilmesi amaçlanmıştır

Cannabinoids: A review neurobiological and neuropsychopharmacological bases of dependence and rewarding effects

Cannabinoids have been associated with a wide range of pharmacological effects, some of which have potential therapeutic benefit while others result in negative outcomes, such as abuse and dependence. Cannabis is the most commonly used illicit substance in the world, but only recently reliable preclinical models have become available for investigating the rewarding and addictive properties of its primary psychoactive constituent, AMetrahydrocannabinol (A9THC). Starting with the discovery of an endogenous brain cannabinoid system with specific receptors and their endogenous ligands, and through the use of the tools such as specific CB1 receptor antagonist, SR141716A, and various transgenic models, considerable advances have been made in understanding the mechanisms underlying cannabinoid dependence. The objective of this review is to evaluate the results of various animal models, such as drug-discrimination, conditioned place preference, self-administration, and precipitated withdrawal, currently in use to facilitate our understanding of the rewarding and addictive properties of cannabinoids, and of the neurobiological mechanisms that may underlie these properties.
PDF

___

  • 1- Hillard CH, Harris RA, Bloom AS. Effects of the cannabinoids on physical properties of brain membranes and phospholipid vesicles: Fluorescence studies. J Pharmacol Exp Ther 1985; 232:579-588.
  • 2- Dewey WL. Cannabinoid pharmacology. Pharmacol Revl 986; 38: 151-178.
  • 3- Howlett AC, Qualy JM, Khachatrial LL. Involvement of Gi in the inhibition of adenylate cyclase by cannabimimetic drugs. Mol Pharm 1986; 29: 307-313.
  • 4- Devane WA, Dysarz FAI, Johnson MR, Melvin LS, Howlett AC. Determination and rization of a cannabinoid receptor in rat brain. Mol Pharm 1988; 34: 605-613.
  • 5- Matsuda LA, Lolait SJ, Brownstein MJ, Young AL, Bonner TA. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990; 346: 561-564.
  • 6- Herkenham M, Lynn AB, Johnson MR et al. Characterization and localization of cannabinoid receptors in rat brain: A quantitative in vitro autoradiographic study. J Neurosci 1991; 11: 563-583.
  • 7- Breivogel CS, Griffin D, Di Marzo V, Martin BR. Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol 2001; 60:155-163.
  • 8- Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 1997; 74: 129-180.
  • 9- Breivogel CS, Childers S.R. The functional neuroanatomy of brain cannabinoid receptors. Neurobiol Dis 1998; 5: 417-431.
  • 10- Munro, S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365: 61-65.
  • 11- Wiley JL. Cannabis: discrimination of "internal bliss". Pharmacol Biochem Behav 1999; 64: 257-260.
  • 12- Alici T, Kayir H, Aygoren MO, Sağlam E, Uzbay IT. Discriminative stimulus properties of tianeptine. Psychopharmacology 2006; 183: 446-451.
  • 13- Prus AJ, Philibin SD, Pehrson AL, Porter JH. Discriminative stimulus properties of the atypical antipsychotic drug clozapine in rats trained to discriminate 1.25 mg/kg clozapine vs. 5.0 mg/kg clozapine vs. vehicle. Behav Pharmacol 2006; 17: 185-194.
  • 14- Uzbay İ.T. Psikofarmakolojinin Temelleri ve Deneysel Araştırma Teknikleri. Ankara: Çizgi Tıp Yayınevi, 2004: 125-128, 153-154.
  • 15- Wiley JL, Huffman JW, Balster RL, Martin BR. Pharmacological specificity of the discriminative stimulus effects of delta-9-tetrahydro-cannabinol in rhesus monkeys. Drug Alcohol Depend 1995; 40: 81-86.
  • 16- Barrett RL, Wiley JL, Balster RL, Martin BR. Pharmacological specificity of the discriminative stimulus effects of delta-9-tetrahydrocan-nabinol in rats. Psychopharmacology 1995; 118:419-424.
  • 17- Compton DR, Johnson MR, Melvin LS, Martin BL. Pharmacological profile of a serious of bycyclic cannabinoid analogs: classification as cannabimimetic agents. J Pharmacol Exp Ther 1992; 260: 201-209.
  • 18- Balster,R.L, Prescott,W.R. Delta-9-tetrahydro-cannabinol discrimination in rats as a model for cannabis intoxication. Neuroscience and behavioral Reviews. 1992; 15:55-62.
  • 19- Wiley JL, Barrett L, Lowe J, Balster RL, Martin BR. Discriminative stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats. Neuropharmacology 1995; 34: 669-676.
  • 20- Perio A, Rinaldi-Carmona M, Maruani J et al. Central medication of the cannabinoid cue: activity of a selective CB1 antagonist, SR141716A. Behav Pharmacol 1996; 7: 65-71.
  • 21- Wiley JL, Golden KM, Ryan WJ et al. Evaluation of cannabimimetic discriminative stimulus effects of anandamide and methylated fluoranandamide in rhesus monkeys. Pharmacol Biochem Behav 1997; 58: 1139-1143.
  • 22- Burkey RT, Nation JR. (R)-Methanandamide, but not anandamide, substitutes for delta-9-THC in drug discrimination procedure. Exp Clin Psychopharmacol 1997; 5: 195-202.
  • 23- Jarbe TU, Lamb RJ, Makriyannis A, Goutopoulos A. Delta-9-THC training dose as determinant for (R)-Methanandamide generalization in rats. Psychopharmacology 1998; 140: 519-522.
  • 24- Alici T, Appel JB. Increasing the selectivity of the discriminative stimulus effects of delta-9-tetrahydrocannabinol: complete substitution with (R)-methanandamide. Pharmacol Biochem Behav 2004; 79: 431-437.
  • 25- Alici T. Increasing the selectivity of the discriminative stimulus effects of delta-9-tetrahyd-rocannabinol. 4th National Congress of Biological Psychiatry. 2003: 167-168.
  • 26- Lepore V, Vorel SR, Lowinson J, Gardner EL. Conditioned place preference induced by delta-9-tetrahydrocannabinol: comparison with cocaine, morphine, and food reward. Life Sci 1995; 56: 2073-2080.
  • 27- Braida D, Pozzi M, Parolaro D, Sala M. Conditioned place preference induced by the cannabinoid agonist CP 55,940: interaction with the opioid system. Neuroscience 2001; 104: 923-926.
  • 28- Mallet P, Beninger RJ. Delta-9-tetrahydro-cannabinol, but not the endogenous ligand anandamide produces conditioned place avoidance. Life Sci 1995; 62: 2431-2439.
  • 29- Valjent E, MaldonadoR. A behavioral model to reveal place preference to delta-9-tet-rahydrocannabinol in mice. Psychopharmacology2000; 147:436-438.
  • 30- Brendson HH, Broekkamp CL Comparison of stimulus properties of fluoxetine and 5-HT receptor agonists in a conditioned taste aversion procedure. Eur J Pharmacol 1994; 253: 83-89.
  • 31- Gardner EL, Vorel SR. Cannabinoid transmission and reward related events. Neurobiol Dis 1998; 5: 502-533.
  • 32- Yokel RA. Intravenous self-administration:response rates, the effects of pharmacological challenges, and drug preference. In: Bozarth, M.A. (ed) Methods of Assessing the Reinforcing Properties of Abused Drugs. New York: Springer, 1987: 1-33.
  • 33- Harris RT, Waters W, Mclendon D. Evulation of reinforcing capability of delta-9-tetrahyd-rocannabinol in monkeys. Psychopharmacologia 1974; 37: 23-29.
  • 34- Mansbach RS, Nicholson KL, Martin BR, Balster RL. Failure of delta-9-tetrahydrocannabinol and CP 55,940 to maintain intravenous self-administration under a fixed-interval schedule in rhesus monkeys. Behav Pharmacol 1994; 5: 219-225.
  • 35- Kaymakçalan S. Physiology and psychological dependence on THC in rhesus monkeys. In: Paton WDM, Crown J (eds) Cannabis and Its derivatives. London: Oxford University Press, 1972:142-149.
  • 36- Pickens R, ThompsonT, Muchow DC. Cannabis and phenylcyclidine self-administrated by animals. In: Goldfarb L, Hoffmeister F (eds) Psychic Dependence (Bayer Symposium IV) New York: Springer, 1973: 78-86.
  • 37- Takahashi RN, Singer G. Effects of body weight levels on cannabis self-administration. Pharmacol Biochem Behav 1980; 13: 877-881.
  • 38- Martellotta MC, Cossu G, Fattore L, Gessa GL, Fratta W. Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drugnaive mice. Neurosicence 1998; 85: 327-330.
  • 39- Braida D, Pozzi M, Parolam D, Sala M. Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940 in the rat: interaction with the opioid system. Eur J Pharmacol 2001; 413: 227-234.
  • 40- Tanda G, Munzar P, Goldberg SR. Self-administration behavior is maintained by the psychoactive ingridient in marijuana in squerrel monkeys. Nature Neurosci 2001; 3: 1073-1074.
  • 41- Cook SA, Lowe JA, Martin BR. CB1 receptor antagonist precipitates withdrawal in mice exposed to delta-9-tetrahydrocannabinol. J Pharm Exp Ther 1998; 285:1150-1156.
  • 42- Justinova Z, Tanda G, Redhi G.H., Goldberg S.R. Self-administration of delta-9-tetrahydro-cannabinol by drug naive squirrel monkeys. Psychopharmacology 2003; 169:135-140.
  • 43- Pierce RC, Kumaresan V. The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse. Neurosci Biobehav Rev 2006; 30: 215-238.
  • 44- Ralevic Y. Cannabinoid modulation of peripheral autonomic and sensory neurotransmission. Eur J Pharmacol 2003; 472: 1-21.
  • 45- Julian MD, Martin AB, Cuellar B. Neuroanatomical relationship between type 1 cannabinoid receptors and dopaminergic systems in the rat basal ganglia. Neuroscience 2003; 119:309-318.
  • 46- Cheer JF, Wassum KM, Heien ML, Phillips PE, Wightman RM. Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. J Neurosci 2004; 24: 4393-4400.
  • 47- Castaneda E, Moss DE, Oddie SD, Whishaw IQ. THC does not affect striatal dopamine relase: microdialysis in freely moving rats. Pharmacol Biochem Behav1991; 40: 587-591.
  • 48- Szabo B, Siemes S, Wallmichrath I. Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids. Eur J Neurosci 2002; 15: 2057-2061.
  • 49- Mas-Nieto M, Pommier B, Tzavara ET et al. Reduction of opioid dependence by the CB1 antagonist SRI 41716A in mice: evaluation of the interest in pharmacotheraphy of opioid addiction. Br. J Pharmacol 2001; 132: 1809-1816.
  • 50- Navarro M, Carrera MR. Fratta W et al. Functional interaction between opioid and cannabinoid receptors in drug self-administration. J. Neurosci 2001; 21: 5344-5350.
  • 51- Swift W, Hall W, Copeland J. One year followup of cannabis dependence among longterm users in Sydney, Australia. Drug Alcohol Depend 2000; 59: 309-318.
  • 52- Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW. Abstinence symptoms following smoked marijuana in humans. Psychopharmacology 1999; 141: 395-404.
  • 53- Jones RT, Benowitz N, Bachman J. Clinical studies of cannabis tolerance and dependence. Ann NY Acad Sci 1976; 282: 221-239.
  • 54- McMillan DE, Dewey WL,Harris LS. Characte-ristics of delta-9-tetrahydrocannabinol tole¬rance. Ann NY Acad Sci USA 1971; 191: 83-99.
  • 55- Aceto M, Scates S, Lowe J, Martin B. Dependence on delta-9-tetrahydrocannabinol: studies on precipitated and abrupt withdrawal. J Pharmacol Exp Ther 1996; 278: 1290-1295.
  • 56- Rinaldi-Carmona M, Barth F, Heulme M.et al. SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 1994; 350: 240-244.
  • 57- Mallet PE, Beninger RJ. The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by delta-9-tetrahydrocannabinol or anandamide. Psychopharmacology 1998; 140: 11-19.
  • 58- Aceto M, Scates S, Lowe J, Martin B. Cannabinoid precipitated withdrawal by the selective cannabinoid receptor antagonist, SR141716A. Eur J Pharmacol 1995; 282: R1-R2.
  • 59- Litchman AH, Seikh SS, Loh HH, Martin BR. Opioid and cannabinoid modulation of precipitated withdrawal in delta-9-tetrahydro-cannabinol and morphine-dependent mice. J Pharmacol Exp Ther 2001; 298:1007-1014.
  • 60- Valverde O, Maldonado R, Valjent E, Zimmer AM, Zimmer A. Cannabinoid withdrawal syndrome is reduced in preproenkephalin knockout mice. J Neurosci 2000; 20: 9284-9289.
  • 61- Aceto MD, Scates SM, Razdan RK, Martin BR. Anandamide, an endogenous cannabinoid, has a very low physical dependence potential. J Pharm Exp Ther 1998; 287: 598-605.
  • 62- Costa B, Giagnoni G, Colleoni M. Precipitated and spontaneous withdrawal in rats tolerant to anandamide. Psychopharmacology 2001; 149: 121-128.
  • 63- Ameri A. The effects of cannabinoids on the brain. Prog Neurobiol 1999; 58: 315-348.
  • 64- Gessa GL, Casu MA, Carta G, Mascia MS. Cannabinoids decrease acetylcholine release in the medial-prefrontal cortex and hippocampus, reversal by SR141716A. Eur J Pharmacol 1998; 355:119-124.
  • 65- Sanudo-Pena M.C, Tsou K, Delay ER et al. Endogenous cannabinoids as an aversive or counter-rewarding system in the rat. Neurosci Lett 1999; 223: 125-128.
  • 66- Navarro M, Chowen J, Rocio A et al. CB1 cannabinoid receptor antagonist-induced opiate withdrawal in morphine-dependent rats. Neuroreport 1998; 9: 3397-3402.
  • 67- Vela G, Ruiz-Gayo M, Fuentes JA. Anandamide decreases naloxone-precipitated withd-rawal signs in mice chronically treated with morphine. Neuropharmacology 1995; 34: 665-668.
  • 68- Thorat SN, Bhargava HN. Evidence for a bidi¬rectional cross-tolerance between morphine and delta-9-tetrahydrocannabinol in mice. Eur J Pharmacol 1994; 260: 5-13.
Bağımlılık Dergisi-Cover
  • ISSN: 1302-5570
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 2000
  • Yayıncı: Galenos Yayınevi
Arşiv
Sayıdaki Diğer Makaleler

İş kazasına bağlı yaralanmalarda alkol kullanımı

Ferruh Niyazi AYOĞLU, Numan KONUK, Sibel KIRAN, Zühtü ŞAHİN, Banu SALTIK, Levent ATİK

Kannabinoidler: Ödüllendirici ve bağımlılık yapıcı etkilerinin nörobiyolojisi ve nöropsikofarmakolojisi üzerine bir gözden geçirme

Tevfik ALICI, Tayfun İ. UZBAY

Tedavi motivasyonu anketi (TMA) türkçe versiyonunun alkol bağımlısı hastalarda faktör yapısı geçerliği ve güvenirliği

Ercan DALBUDAK, Ömer SAATÇİOÜLU, Birim S. DANIŞMANT, Richard M. RYAN, Duran ÇAKNAK, Cüneyt EVREN

Gamma glutamil transferaz düzeyi yüksek alkol bağımlılarının özellikleri

Ö. Ayhan KALYONCU, Özgür ÖZTÜRK, Gültürk KÖROĞLU, Yasin GENÇ, Devran TAN, Hasan MIRSAL, Özkan PEKTAŞ, Mansur BEYAZYÜREK

Tıp fakültesi birinci ve ikinci sınıf öğrencilerinde sigara içme durumu ve depresyon yaygınlığı arasındaki ilişki

Saniye ÖZDEMİR, Şule ŞAHSIVAR, Selma ÇİVİ, Kamile MARAKOĞLU