Importance of D(1) receptors for associative components of amphetamine-induced behavioral sensitization and conditioned activity: a study using D(1) receptor knockout mice.
BACKGROUND
Repeated exposure to psychostimulant drugs results in conditioned activity and behavioral sensitization. Nonassociative cellular changes are necessary for behavioral sensitization, while associative processes appear to modify the sensitized response.


OBJECTIVE
The purpose of the present study was to determine whether the absence of the D(1) receptor would disrupt associative processes modulating sensitization and conditioned activity.


METHODS
Wild-type and D(1) receptor knockout mice (i.e., D(1)-deficient mice) were injected with amphetamine (AMPH; 8 mg/kg, IP) before being placed in a previously novel test chamber (AMPH-Test group) or before being returned to the home cage (AMPH-Home group). Separate groups of mice were injected with saline (SAL) at the same time points. Distance traveled was measured 60 min each day, with the preexposure phase lasting 1 or 7 days. Sensitization was subsequently assessed after an injection of AMPH (1 mg/kg, IP), while conditioned activity was assessed after an injection of SAL.


RESULTS
After a 1-day preexposure phase, wild-type and D(1)-deficient mice exhibited similar patterns of sensitization and conditioned activity. After a 7-day preexposure phase, (1) D(1)-deficient mice exhibited more robust context-specific sensitization than wild-type mice, (2) only D(1)-deficient mice showed context-independent sensitization, and (3) only D(1)-deficient mice showed conditioned activity.


CONCLUSIONS
Repeatedly treating D(1)-deficient mice with AMPH appears to cause a general increase in responsivity. The reason for this hyper-responsivity is uncertain, but it is possible that cues from the testing environment were unable to inhibit responding (i.e., associative processes were disrupted). Alternatively, compensatory mechanisms (e.g., increases in D(2)-like receptors) may affect processes underlying sensitization and conditioned activity.
McDougall
Sanders A
SA
Department of Psychology, California State University, San Bernardino, CA 92407, USA. smcdouga@csusb.edu
Reichel
Carmela M
CM
Cyr
Michelle C
MC
Karper
Patrick E
PE
Nazarian
Arbi
A
Crawford
Cynthia A
CA
D000661:Amphetamine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants; D003213:Conditioning, Psychological / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D013997:Time Factors
D000697:Central Nervous System Stimulants; D017447:Receptors, Dopamine D1; D000661:Amphetamine