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Preclinical Pharmacology and Toxicology

Addiction

  •  Sensitization to locomotor activity stimulation in mouse
  • Other tests that can be set up: spontaneous and induced withdrawal signs in mouse or rat, place preference in rat, drug discrimination in rat, self-administration in rat

We used gross observation, locomotor activity, and drug discrimination to evaluate compounds for therapeutic potential against cocaine addiction under two NIDA grants, 1998-2002.

James L. Howard was President of the Society for the Stimulus Properties of Drugs, 1983-1984.

Publications

Howard, J.L., Jones, C.N., & McBennett, S.T. (1978). Discriminative stimulus properties of antidepressants. In Colpaert, F.C., & Rosecrans, J.A. (Eds.), Stimulus Properties of Drugs: Ten Years of Progress (pp.157-166). Amsterdam: Elsevier/North Holland Biomedical Press.

Jones, C.N., Howard, J.L., & McBennett, S.T. (1979). Stimulus properties of antidepressants in the rat. Psychopharmacology, 67, 111-118.

Craft, R.M., & Howard, J.L. (1988). Cue properties of oral and transdermal nicotine in the rat. Psychopharmacology, 96, 281-284.

Carroll, F.I., Pawlush, N., Kuhar, M.J., Pollard, G.T., & Howard, J.L. (2004). Sythesis, monoamine transporter binding properties, and behavioral pharmacology of a series of 3beta-(substituted phenyl)-2beta-(3'-substituted isoxoxoazol-5-yl)tropanes. Journal of Medicinal Chemistry, 47, 296-302.

Carroll, F.I., Thomas, J.B., Dykstra, L.A., Granger, A.L., Allen, R.M., Howard, J.L., Pollard, G.T., Aceto, M.D., & Harris, L.S. (2004). Pharmacological properties of JDTic: A novel k opioid receptor antagonist. European Journal of Pharmacology, 501, 111-119.

Carroll, F.I., Runyon, S.P., Abraham, P., Navarro, H., Kuhar, M.J., Pollard, G.T., & Howard, J.L. (2004). Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted phenyl)tropane-2-carboxylic acid methyl ester isomers. Journal of Medicinal Chemistry, 47, 6401-6409.

Beardsley, P.M., Howard, J.L., Shelton, K.L., & Carroll, F.I. (2005). Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock-stressors vs cocaine-primes and its antidepressant-like effects in rats. Psychopharmacology, 183, 118-126.

Carroll, F.I., Howard, J.L., Howell, L.L., Fox, B.S., & Kuhar, M.J. (2006). Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse. AAPS Journal, 8, E196-203.  Reprinted as Chapter 12 of Rapaka, R.S. & Sadee, W. (Eds.), Drug Addiction:  From Basic Research to Therapy (pp. 179-191).  New York:  Springer, 2008.

Carroll, F.I., Fox, B.S., Kuhar, M.J., Howard, J.L., Pollard, G.T., & Schenk, S. (2006). Effects of dopamine transporter selective 3-phenyltropane analogues on locomotor activity, drug discrimination, and cocaine self administration after oral administration. European Journal of Pharmacology, 553, 149-156.

Navarro, H.A., Howard, J.L., Pollard, G.T., & Carroll, F.I. (2009).  Positive allosteric modulation of the human cannabinoid (CB1) receptor by RTI-371, a selective inhibitor of the dopamine transporter.  British Journal of Pharmacology, 156, 1178-1184. 

Beardsley, P.M., Pollard, G.T., Howard, J.L., & Carroll, F.I. (2010).  Effectiveness of analogues of the kappa opioid receptor antagonist (3R)-7-hydroxy-N-((1S)-{[(3R,4R)-4-(3-hydroxyphenyl)-1-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic) to reduce U50,488-induced diuresis and stress-induced cocaine reinstatement in rats.  Psychopharmacology, 210, 189-198.

Runyon, S.P., Brieaddy, L.E., Mascarella, S.W., Thomas, J.B., Navarro, H.A., Howard, J.L., Pollard, G.T., & Carroll, F.I. (2010).  Analogues of (3R)-7-hydroxy-N-[(1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamine (JDTic).  Synthesis and in vitro and in vivo opioid receptor antagonist activity.  Journal of Medicinal Chemistry, 53, 5290-5301.