Keith L. Shelton, Ph.D.
Department: Department of Pharmacology and Toxicology
Phone: (804) 827-2104
Fax: (804) 828-2117
Robert Blackwell Smith Building, Room 760D
410 North 12th Street
Richmond, Virginia 23298
- Virginia Commonwealth University, 1995
- Behavioral pharmacology of abused inhalants, stimulants and alcohol
- Neurochemical mechanisms of subjective drug effects
- Behavioral mechanisms of relapse to drug taking
Alone, and in collaboration with other researchers, my laboratory examines many different behavioral effects of abused drugs. One of the current major projects involves abused inhalants. Abuse of inhalants such as motor fuels, solvent mixtures and gases is a major public health concern both in the U.S. and worldwide, especially in children and adolescents.
Despite the magnitude of the problem, little is known about the neurochemical systems responsible for producing the intoxicating effects of these commonly available products. To address this issue, my laboratory is examining the neurochemical systems underlying the subjective effects of inhalants using the drug discrimination model in mice.
Although the drug discrimination paradigm is used by many researchers, we are currently the only laboratory using this model with abused inhalants. Drug discrimination is a learned operant task that is believed to model the intoxicating effects of drugs in humans. This paradigm involves repeated pairings of drug or vehicle exposures with different responses in order to gain access to a reinforcer. In our case, we train mice to discriminate inhalant exposure from air exposure. Over a number of experimental sessions, the mice learn which lever will produce a reinforcer based on the subjective state induced by the inhalant. Once the mice are trained, there are a number of different questions which can be addressed. For instance, inhalants from other classes can be examined to determine if they produce effects similar to the trained inhalant. This should allow us to group inhalants according to their discriminative stimulus profiles and potentially predict if newly marketed products are likely to be abused in a manner similar to ones we have trained. At a more basic level, we can also explore whether drugs with known actions on specific neurotransmitter systems have effects like those of the trained inhalants. Understanding how these compounds produce their subjective effects is likely to be one of the key aspects necessary in developing effective treatments for curbing their abuse.
Shelton KL and Nicholson KL. (2010) GABA(A) positive modulator and NMDA antagonist-like discriminative stimulus effects of isoflurane vapor in mice. Psychopharmacology (Berl). 212(4):559-69.
Beardsley PM, Shelton KL, Hendrick E and Johnson KW. (2010) The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse. European Journal of Pharmacology. 637(1-3):102-8.
Shelton KL. (2010) Pharmacological characterization of the discriminative stimulus of inhaled 1,1,1-trichloroethane. Journal of Pharmacology and Experimental Therapeutics. 333(2):612-20.
Shelton KL and Slavova-Hernandez G. (2009) Characterization of an inhaled toluene drug discrimination in mice: effect of exposure conditions and route of administration. Pharmacology, Biochemistry and Behavior. 92(4): 614-620.
Shelton KL. (2009) Discriminative stimulus effects of inhaled 1,1,1-trichloroethane in mice: comparison to other hydrocarbon vapors and volatile anesthetics. Psychopharmacology. 203(2): 431-440.