Planarians have mammalian-like neurotransmitter systems
and have been established as a novel in
vivo model for neuropharmacology. In previous research, planarians that
have been exposed to the cannabinoid receptor (CB-R) agonist WIN 55,212-2 for 1
h displayed abstinence-induced withdrawal when tested in drug-free, but not in
drug-containing, water. The goals of the present study were to extend previous
work and to further establish a cannabinoid behavioral model with planarians.
The results showed 1) four different CB-R antagonists (AM251, AM281, SLV319 and
SR144528) dose-relatedly blocked development of physical dependence induced by
two different CB-R agonists (WIN 55,212-2 and JWH251); 2) none of the same four antagonists (AM251, AM281, SLV319 or SR144528)
precipitated withdrawal; 3) short wavelength (254
nm), but not long wavelength (366 nm), ultraviolet (UV) light attenuated
abstinence-induced withdrawal from WIN 55,212-2, while short wavelength UV
light induced moderate withdrawal behavior. The results confirm the use of a
planarian model as a simple yet robust way to study development of physical
dependence to cannabinoid agonists. The effect of UV irradiation adds to the
evidence that the results are receptor-related. The results also give rise to
the surprising suggestion, within the limitations of the methodology, that
development of cannabinoid physical dependence and antagonist-induced
precipitated withdrawal might be separable phenomena in planarians.
References
[1]
Raffa, R.B. (2008) Planaria: A Model for Drug Action and Abuse. CRC Press, Austin TX, 150 p. https://doi.org/10.1201/9781498713597
[2]
Palladini, G., Margotta, V., Carolei, A. and Hernandez, M.C. (1980) Dopamine Agonist Performance in Planaria after Manganese Treatment. Experientia, 36, 449-450. http://www.ncbi.nlm.nih.gov/pubmed/7379922 https://doi.org/10.1007/BF01975141
[3]
Passarelli, F., Merante, A., Pontieri, F.E., Margotta, V., Venturini, G. and Palladini, G. (1999) Opioid-Dopamine Interaction in Planaria: A Behavioral Study. Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology, 124, 51-55. http://www.ncbi.nlm.nih.gov/pubmed/10579648 https://doi.org/10.1016/S0742-8413(99)00048-1
[4]
Buttarelli, F.R., Pellicano, C. and Pontieri, F.E. (2008) Neuropharmacology and Behavior in Planarians: Translations to Mammals. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 147, 399-408. https://doi.org/10.1016/j.cbpc.2008.01.009
[5]
Pagán, O.R., Montgomery, E., Deats, S., Bach, D. and Baker, D. (2015) Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians. Neurochemical Research, 40, 2087-2090. https://doi.org/10.1007/s11064-015-1512-6
[6]
Bach, D.J., Tenaglia, M., Baker, D.L., Deats, S., Montgomery, E. and Pagán, O.R. (2016) Cotinine Antagonizes the Behavioral Effects of Nicotine Exposure in the Planarian Girardiatigrina. Neuroscience Letters, 632, 204-208. https://doi.org/10.1016/j.neulet.2016.09.005
[7]
Raffa, R.B., Holland, L.J. and Schulingkamp, R.J. (2001) Quantitative Assessment of Dopamine D2 Antagonist Activity Using Invertebrate (Planaria) Locomotion as a Functional Endpoint. Journal of Pharmacological and Toxicological Methods, 45, 223-226. http://www.ncbi.nlm.nih.gov/pubmed/11755386 https://doi.org/10.1016/S1056-8719(01)00152-6
[8]
Raffa, R.B. and Valdez, J.M. (2001) Cocaine Withdrawal in Planaria. European Journal of Pharmacology, 430, 143-145. http://www.ncbi.nlm.nih.gov/pubmed/11698074 https://doi.org/10.1016/S0014-2999(01)01358-9
[9]
Raffa, R.B., Stagliano, G.W. and Umeda, S. (2003) Kappa-Opioid Withdrawal in Planaria. Neuroscience Letters, 349, 139-142. http://www.ncbi.nlm.nih.gov/pubmed/12951188 https://doi.org/10.1016/S0304-3940(03)00814-0
[10]
Raffa, R.B., Cavallo, F. and Capasso, A. (2007) Flumazenil-Sensitive Dose-Related Physical Dependence in Planarians Produced by Two Benzodiazepine and One Non-Benzodiazepine Benzodiazepine-Receptor Agonists. European Journal of Pharmacology, 564, 88-93. https://doi.org/10.1016/j.ejphar.2007.02.006
[11]
Maldonado, R., Valverde, O. and Berrendero, F. (2006) Involvement of the Endocannabinoid System in Drug Addiction. Trendsin Neurosciences, 29, 225-232. https://doi.org/10.1016/j.tins.2006.01.008
[12]
Diana, M., Melis, M., Muntoni, A.L. and Gessa, G.L. (1998) Mesolimbic Dopaminergic Decline after Cannabinoid Withdrawal. Proceedings of National Academy of Sciences of USA, 95, 10269-10273. http://www.ncbi.nlm.nih.gov/pubmed/9707636 https://doi.org/10.1073/pnas.95.17.10269
[13]
Aceto, M.D., Scates, S.M. and Martin, B.B. (2001) Spontaneous and Precipitated Withdrawal with a Synthetic Cannabinoid, WIN 55212-2. European Journal of Pharmacology, 416, 75-81. http://www.ncbi.nlm.nih.gov/pubmed/11282115
https://doi.org/10.1016/S0014-2999(01)00873-1
[14]
Buttarelli, F.R., Pontieri, F.E., Margotta, V. and Palladini, G. (2002) Cannabinoid-Induced Stimulation of Motor Activity in Planaria through an Opioid Receptor-Mediated Mechanism. Progress in Neuropsychopharmacology Biological Psychiatry, 26, 65-68. http://www.ncbi.nlm.nih.gov/pubmed/11853121
[15]
Rawls, S.M., Rodriguez, T., Baron, D.A. and Raffa, R.B. (2006) A Nitric Oxide Synthase Inhibitor (L-NAME) Attenuates Abstinence-Induced Withdrawal from Both Cocaine and a Cannabinoid Agonist (WIN 55212-2) in Planaria. Brain Research, 1099, 82-87. https://doi.org/10.1016/j.brainres.2006.04.103
[16]
Cosenza, M., Gifford, A.N., Gatley, S.J., Pyatt, B., Liu, Q., Makriyannis, A. and Volkow, N.D. (2000) Locomotor Activity and Occupancy of Brain Cannabinoid CB1 Receptors by the Antagonist/Inverse Agonist AM281. Synapse, 38, 477-482. https://doi.org/10.1002/1098-2396(20001215)38:4<477::AID-SYN13>3.0.CO;2-Y
[17]
Howlett, A.C., et al. (2002) International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors. Pharmacological Reviews, 54, 161-202. http://pharmrev.aspetjournals.org https://doi.org/10.1124/pr.54.2.161
[18]
Furchgott, R.F., Ehrreich, S.J. and Greenblatt, E. (1961) The Photoactivated Relaxation of Smooth Muscle of Rabbit Aorta. The Journal of General Physiology, 44, 499-519. http://www.ncbi.nlm.nih.gov/pubmed/13702637 https://doi.org/10.1085/jgp.44.3.499
[19]
Tallarida, R.J., Sevy, R.W., Harakal, C. and Loughnane, M.H. (1975) Characteristics of Photorelaxation in Vascular Smooth Muscle: Evidence Supporting the Hypothesis of Drug-Receptor Equilibrium Disturbance. IEEE Transactions on Biomedical Engineering, 22, 493-501. http://www.ncbi.nlm.nih.gov/pubmed/241702 https://doi.org/10.1109/TBME.1975.324471
[20]
Raffa, R.B., Valdez, J.M., Holland, L.J. and Schulingkamp, R.J. (2000) Energy-Dependent UV Light-Induced Disruption of (-)sulpiride Antagonism of Dopamine. European Journal of Pharmacology, 406, R11-R12. http://www.ncbi.nlm.nih.gov/pubmed/11040357 https://doi.org/10.1016/S0014-2999(00)00730-5
[21]
Rawls, S.M., Gomez, T. and Raffa, R.B. (2007) An NMDA Antagonist (LY 235959) Attenuates Abstinence-Induced Withdrawal of Planarians Following Acute Exposure to a Cannabinoid Agonist (WIN 55212-2). Pharmacology Biochemistry and Behavior, 86, 499-504. https://doi.org/10.1016/j.pbb.2007.01.010
[22]
Raffa, R.B., Stagliano, G.W. and Tallarida, R.J. (2006) Subadditive Withdrawal from Cocaine/κ-Opioid Agonist Combinations in Planaria. Brain Research, 1114, 31-35. https://doi.org/10.1016/j.brainres.2006.07.037
[23]
Pagán, O.R. (2017) Planaria: An Animal Model That Integrates Development, Regeneration and Pharmacology. The International Journal of Developmental Biology, 61, 519-529. https://doi.org/10.1387/ijdb.160328op
[24]
Rinaldi-Carmona, M., et al. (1998) SR 144528, the First Potent and Selective Antagonist of the CB2 Cannabinoid Receptor. Journal of Pharmacology and Experimental Therapeutics, 284, 644-650. http://www.ncbi.nlm.nih.gov/pubmed/9454810
[25]
Sagredo, O., et al. (2009) Cannabinoid CB2 Receptor Agonists Protect the Striatum against Malonate Toxicity: Relevance for Huntington’s Disease. Glia, 57, 1154-1167. https://doi.org/10.1002/glia.20838
[26]
Landry, R.P., Martinez, E., DeLeo, J.A. and Romero-Sandoval, E.A. (2012) Spinal Cannabin-oid Receptor Type 2 Agonist Reduces Mechanical Allodynia and Induces Mitogen-Activated Protein Kinase Phosphatases in a Rat Model of Neuropathic Pain. The Journal of Pain, 13, 836-848. https://doi.org/10.1016/j.jpain.2012.05.013
[27]
Raffa, R.B., Dasrath, C.S. and Brown, D.R. (2003) Disruption of a Drug-Induced Choice Behavior by UV Light. Behavioural Pharmacology, 14, 569-571. https://doi.org/10.1097/00008877-200311000-00010
[28]
Ramoz, L., et al. (2012) Mephedrone (“Bath Salt”) Pharmacology: Insights from Invertebrates. Neuroscience, 208, 79-84. https://doi.org/10.1016/j.neuroscience.2012.01.019
[29]
Beaven, G.H. and Holiday, E.R. (1952) Ultraviolet Absorption Spectra of Proteins and Amino Acids. Advances in Protein Chemistry, 7, 319-386. http://www.ncbi.nlm.nih.gov/pubmed/14933256 https://doi.org/10.1016/S0065-3233(08)60022-4
