Drug Addiction-the Neurochemical Perspective of Brain in Drug-Seeking Behavior

SHI-KWANG LIN^1,2, SHIAO-HUA WU¹, YA-SHU YANG² AND WYNN H.T. PAN^1*

^1. Institute of Pharmacology, Yang Ming University, 155, Sec. 2, Linong St., Beitou District, Taipei City 112, Taiwan (R.O.C.)
^2. Department of Adult Psychiatry, Taipei City Psychiatric Center, 309 Songde Rd., Sinyi District, Taipei City 110, Taiwan (R.O.C.)

(Received: May 7, 2003; Accepted: July 14, 2003)

   A critical challenge of the investigation in the neurobiological mechanism of drug addiction is how acute actions become transformed into chronic effects that underlie the compulsive drug-seeking and craving in addiction. Repeated administrations of psychostimulants can enhance the behavioral response upon reinstatement of the drug, a prominent phenomenon known as behavioral sensitization. It has been implicated that the neuronal changes brought about by sensitization in the mesocorticolimbic pathways have close relationship with compulsive drug seeking in addicts. Dopamine and glutamate are the two major neurotransmitters involved in the sensitization of abused drugs. The authors reviewed literature pertinent to amphetamine and cocaine addiction in order to address the recent important concepts and findings in dopaminergic and glutamatergic neurochemical systems of mesolimbic and mesocortical circuits associated with drug-related behavior. The present review also discusses the role of associative learning as manifested in the relationship between environmental cues of drug administration and intractable drug-seeking behavior.

Key words: addiction, drug-seeking behavior, sensitization, dopamine, glutamate, nucleus accumbens, ventral tegmental area, associative learning