alexa Self-Administration of an Endogenous Cannabinoid 2-Arachidonoylglycerol in Experimentally Naïve Rats | Open Access Journals
ISSN: 2329-6488
Journal of Alcoholism & Drug Dependence
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Self-Administration of an Endogenous Cannabinoid 2-Arachidonoylglycerol in Experimentally Naïve Rats

Takato Hiranita*

Division of Neurotoxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, Jefferson, AR 72079-9501, USA

Corresponding Author:
Takato Hiranita
Division of Neurotoxicology,
National Center for Toxicological Research (NCTR),
U.S. Food and Drug Administration (FDA),
3900 NCTR Road, Jefferson, AR 72079-9501, USA
Tel: +61-3-9214-5596, +61-3-5327-6335
E-mail: [email protected]

Received date: October 08, 2015 Accepted date: October 13, 2015 Published date: October 17, 2015

Citation: Hiranita T (2015) Self-Administration of an Endogenous Cannabinoid 2-Arachidonoylglycerol in Experimentally Naïve Rats. J Alcohol Drug Depend 3:e126. doi:10.4172/2329-6488.1000e126

Copyright: © 2015 Hiranita T. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Alcoholism & Drug Dependence

A recent study by Dr. Maria Antonietta De Luca demonstrated intravenous (IV) self-administration responding (nose-poking) of an endogenous compound in an experimentally naïve, adult rat species [1]. Surprisingly, response-dependent changes of visual stimulus were not presented in the study when the compound was injected. This finding is very unique since there is few if any endogenous compounds that have been reported to maintain self-administration responding above vehicle levels through an IV route of administration (i.e. not intracranial self-injections) in rodent species. Further, it is also likely that a phytocannabinoid (−)-trans-Δ9-tetrahydrocannabinol (Δ9- THC, Figure 1), a primary psychoactive constituent in marijuana, is not an effective reinforcer in rat [2,3] and rhesus monkey species [4-6] relative to standard drugs of abuse [7].

alcoholism-drug-dependence-Chemical-structures-2-arachidonoylglycerol

Figure 1: Chemical structures of 2-arachidonoylglycerol (1,3-dihydroxy- 2-propanyl (5Z,8Z,11Z,14Z)-5,8,11,14-eicosatetraenoate) and (−)-trans-Δ9- tetrahydrocannabinol [(−)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro- 6H-benzo[c]chromen-1-ol].

The use of marijuanahas been legalized in two states of the U.S as of today. Despite high effectiveness of Δ9-THC in experimentally naïve squirrel monkeys [8], Δ9-THC has been reported to fail to maintain IV self-administration responding above vehicle levels in rats [2,3] and rhesus monkeys [4-6]. On the other hand, there continues to be an increase in the abuseand non-medical use of a number of ‘designer’ drugs [9-11]. Among these drugs are synthetic cannabinoids that are frequently found in many K2/Spice preparations [9-11]. Several synthetic cannabinoids have been found to maintain IV self-administration responding in experimentally naïve rats [12-16], and mice [17-20]. For endocannabinoids, only anandamide has been demonstrated to maintain IV self-administration responding in a squirrel monkey species [21]. However, the sample size was only one to draw any conclusion [21]. Using IV drug self-administration procedures in squirrel monkeys, another endocannabinoid 2-arachidonoylglycerol (Figure 1) has been shown to substitute for anandamide or (-)-nicotine [22]. These findings may suggest the reinforcing effects of endocannabinoid in rats. Importantly, the IV selfadministration of endocannabinoid anandamide in an experimentally naïve squirrel monkey [21] and of synthetic cannabinoids in experimentally naïve rats [13,14] and mice [17,19,20] occurred when response-dependent changes of visual stimulus were presented. Despite the low effectiveness of phytocannabinoid Δ9-THC in rats as a positive reinforcer and a lack of response-dependent changes of visual stimulus, the endocannabinoid 2-arachidonoylglycerol maintained IV self-administration responding above vehicle levels in all six of six experimentally naïve rats assessed (i.e., 100% of rats assessed) [1]. The finding should be appreciated because endogenous monoamine dopamine, an important neurotransmitter for induction of reinforcing effects of stimulants [23,24], failed to maintain IV self-administration responding above vehicle levels when substituted for (-)-cocainein rats [25]. Further, a dopamine D2-like agonist quinpirole has been found to fail to induce IV self-administration responding above vehicle levels in experimentally naïve rats even when a response-dependent injection-paired visual stimulus was presented [26,27]. In addition, (-)-nicotinehas been found to fail to induce IV self-administration responding above vehicle levels in experimentally naïve rats when an injection-paired visual stimulus was absent [28]. Finally a synthetic cannabinoidWIN 55,212-2 was reinforcing in only a maximum of 85.7% of experimentally naïve rats assessed (=12/14) among a range of several injection doses [13]. Thus it appears that the endocannabinoid 2-arachidonoylglycerolis a relatively effective positive reinforcer in rats.

As mentioned above, the abuse of synthetic cannabinoids is increasing [9,10]. Despite the low effectiveness of a phytocannabinoid Δ9-THC in a rat species [2,3], Dr. De Luca found a relatively high capacity of an endocannabinoid 2-arachidonoylglycerol to induce reinforcing effects in experimentally naïve rats [1]. The selfadministration model of 2-arachidonoylglycerol may be useful to study pharmacology of endocannabinoids. In addition, the finding may lead to further development of medications for cannabinoid abuse in humans using a rat species.

Acknowledgements

The present work was supported by the Division of Neurotoxicology/ NCTR/U.S. FDA. The information in the present article is not a formal dissemination of information by the FDA and does not represent agency position or policy.

References

  1. De Luca MA, Valentini V, Bimpisidis Z, Cacciapaglia F, Caboni P, et al. (2014) Endocannabinoid 2-Arachidonoylglycerol Self-Administration by Sprague-Dawley Rats and Stimulation of in vivo Dopamine Transmission in the Nucleus Accumbens Shell. Front Psychiatry 5: 140.
  2. Cha HJ, Lee KW, Song MJ, Hyeon YJ, Hwang JY, et al. (2014) Dependence Potential of the Synthetic Cannabinoids JWH-073, JWH-081, and JWH-210: In Vivo and In Vitro Approaches. Biomol Ther (Seoul) 22: 363-369.
  3. Lefever TW, Marusich JA, Antonazzo KR, Wiley JL (2014) Evaluation of WIN 55,212-2 self-administration in rats as a potential cannabinoid abuse liability model. Pharmacol Biochem Behav 118: 30-35.
  4. Mansbach RS, Nicholson KL, Martin BR, Balster RL (1994) Failure of Delta(9)-tetrahydrocannabinol and CP 55,940 to maintain intravenous self-administration under a fixed-interval schedule in rhesus monkeys. Behav Pharmacol 5: 219-225.
  5. Harris RT, Waters W, McLendon D (1974) Evaluation of reinforcing capability of delta-9-tetrahydrocannabinol in rhesus monkeys. Psychopharmacologia 37: 23-29.
  6. Carney JM, Uwaydah IM, Balster RL (1977) Evaluation of a suspension system for intravenous self-administration studies of water-insoluble compounds in the rhesus monkey. Pharmacol Biochem Behav 7: 357-364.
  7. Hiranita T, Kohut SJ, Soto PL, Tanda G, Kopajtic TA, et al. (2014) Preclinical efficacy of N-substituted benztropine analogs as antagonists of methamphetamine self-administration in rats. J Pharmacol Exp Ther 348: 174-191.
  8. Justinova Z, Panlilio LV, Moreno-Sanz G, Redhi GH, Auber A, et al. (2015) Effects of Fatty Acid Amide Hydrolase (FAAH) Inhibitors in Non-Human Primate Models of Nicotine Reward and Relapse. Neuropsychopharmacology 40: 2185-2197.
  9. Seely KA, Lapoint J, Moran JH, Fattore L (2012) Spice drugs are more than harmless herbal blends: A review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuropsychopharmacol Biol Psychiatry 39: 234-243.
  10. Papanti D, Schifano F, Botteon G, Bertossi F, Mannix J, et al. (2013) "Spiceophrenia": A systematic overview of "spice"-related psychopathological issues and a case report. Hum Psychopharmacol 28: 379-389.
  11. Baumann MH, Solis E Jr, Watterson LR, Marusich JA, Fantegrossi WE, et al. (2014) Baths salts, spice, and related designer drugs: The science behind the headlines. J Neurosci 34: 15150-15158.
  12. De Luca MA, Bimpisidis Z, Melis M, Marti M, Caboni P, et al. (2015) Stimulation of in vivo dopamine transmission and intravenous self-administration in rats and mice by JWH-018, a Spice cannabinoid. Neuropharmacology 99: 705-714.
  13. Fattore L, Cossu G, Martellotta CM, Fratta W (2001) Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats. Psychopharmacology (Berl) 156: 410-416.
  14. Spano MS, Fattore L, Cossu G, Deiana S, Fadda P, et al. (2004) CB1 receptor agonist and heroin, but not cocaine, reinstates cannabinoid-seeking behaviour in the rat. Br J Pharmacol 143: 343-350.
  15. Flores Á, Maldonado R, Berrendero F (2014) The hypocretin/orexin receptor-1 as a novel target to modulate cannabinoid reward. Biol Psychiatry 75: 499-507.
  16. Lecca D, Cacciapaglia F, Valentini V, Di Chiara G (2006) Monitoring extracellular dopamine in the rat nucleus accumbens shell and core during acquisition and maintenance of intravenous WIN 55,212-2 self-administration. Psychopharmacology (Berl) 188: 63-74.
  17. Navarro M, Carrera MR, Fratta W, Valverde O, Cossu G, et al. (2001) Functional interaction between opioid and cannabinoid receptors in drug self-administration. J Neurosci 21: 5344-5350.
  18. Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, et al. (1999) Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283: 401-404.
  19. Mendizábal V, Zimmer A, Maldonado R (2006) Involvement of kappa/dynorphin system in WIN 55,212-2 self-administration in mice. Neuropsychopharmacology 31: 1957-1966.
  20. Martellotta MC, Cossu G, Fattore L, Gessa GL, Fratta W (1998) Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drug-naive mice. Neuroscience 85: 327-330.
  21. Justinova Z, Solinas M, Tanda G, Redhi GH, Goldberg SR (2005) The endogenous cannabinoid anandamide and its synthetic analog R(+)-methanandamide are intravenously self-administered by squirrel monkeys. J Neurosci 25: 5645-5650.
  22. Justinová Z, Yasar S, Redhi GH, Goldberg SR (2011) The endogenous cannabinoid 2-arachidonoylglycerol is intravenously self-administered by squirrel monkeys. J Neurosci 31: 7043-7048.
  23. Hiranita T, Mereu M, Soto PL, Tanda G, Katz JL (2013) Self-administration of cocaine induces dopamine-independent self-administration of sigma agonists. Neuropsychopharmacology 38: 605-615.
  24. Hiranita T, Soto PL, Tanda G, Kopajtic TA, Katz JL (2013) Stimulants as specific inducers of dopamine-independent σ agonist self-administration in rats. J Pharmacol Exp Ther 347: 20-29.
  25. Pilla M, Perachon S, Sautel F, Garrido F, Mann A, et al. (1999) Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature 400: 371-375.
  26. Collins GT, Woods JH (2007) Drug and reinforcement history as determinants of the response-maintaining effects of quinpirole in the rat. J Pharmacol Exp Ther 323: 599-605.
  27. Collins GT, Woods JH (2009) Influence of conditioned reinforcement on the response-maintaining effects of quinpirole in rats. Behav Pharmacol 20: 492-504.
  28. Palmatier MI, Evans-Martin FF, Hoffman A, Caggiula AR, Chaudhri N, et al. (2006) Dissociating the primary reinforcing and reinforcement-enhancing effects of nicotine using a rat self-administration paradigm with concurrently available drug and environmental reinforcers. Psychopharmacology (Berl) 184: 391-400.
Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Recommended Conferences

Article Usage

  • Total views: 11787
  • [From(publication date):
    October-2015 - Nov 20, 2017]
  • Breakdown by view type
  • HTML page views : 7964
  • PDF downloads : 3823
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords