Behavioral sensitization is a long lasting type of behavioral plasticity that occurs after repeated exposure to psychostimulant drugs (e.g., amphetamine and cocaine). This phenomenon has been studied intensively because of its utility as an animal model of psychosis and drug addiction. To date, most of the research on behavioral sensitization has shown that the dopamine (DA) neurotransmitter system is critically involved. Specifically, this research has revealed that drugs capable of blocking DA D1A and D5 receptors will prevent the occurrence of behavioral sensitization. Unfortunately, differentiating between the D1A and D5 receptor has proven to be an almost intractable problem, since no drug is yet available that can exclusively block one of these receptors without affecting the other. To get around this problem, I propose to use the D1A deficient mouse (a mouse that does not produce the D1A receptor) to determine the importance of the D1A receptor for behavioral sensitization. This proposal has the following specific aims: 1) to determine if the D1A receptor is necessary for the induction (i.e., initial development) of amphetamine-induced sensitization; 2) to determine if the D1A receptor is necessary for the long-term expression of amphetamine-induced sensitization; 3) to determine if the neuronal changes that mediate amphetamine-induced sensitization are produced by an NMDA-mediated modulation of D1A receptors; and 4) to determine if developmental compensation is important for amphetamine-induced sensitization in the D1A deficient mouse.
| McDougall, Sanders A; Reichel, Carmela M; Cyr, Michelle C et al. (2005) Importance of D(1) receptors for associative components of amphetamine-induced behavioral sensitization and conditioned activity: a study using D(1) receptor knockout mice. Psychopharmacology (Berl) 183:20-30 |
| Sicotte, Nancy L; Voskuhl, Rhonda R; Bouvier, Seth et al. (2003) Comparison of multiple sclerosis lesions at 1.5 and 3.0 Tesla. Invest Radiol 38:423-7 |
| Karper, Patrick E; De la Rosa, Herminia; Newman, Eva R et al. (2002) Role of D1-like receptors in amphetamine-induced behavioral sensitization: a study using D1A receptor knockout mice. Psychopharmacology (Berl) 159:407-14 |
