Behavioral effects of cocaine on a transgenic mouse model of cortical-limbic compulsion.
We previously created a transgenic mouse model of cortical-limbic induced compulsions in which dopamine D1 receptor-expressing (D1+) neurons in restricted regional subsets of the cortex and amygdala express a neuropotentiating cholera toxin (CT) transgene. These 'D1CT' mice engage in complex behavioral abnormalities uniquely resembling human compulsions, such as non-aggressive biting of cagemates during grooming, repeated leaping and episodes of perseverance of any and all normal behaviors. Because both compulsions and cocaine-induced behaviors may represent forms of psychomotor activation that have a shared or overlapping neurological basis, we have examined the behavioral response of these 'compulsive' mice to cocaine. In both control and D1CT mice, cocaine increased the amount of time spent engaged in typical cocaine-dependent stereotypies such as locomotion, sniffing, or gnawing, while the remainder of behaviors within their normally complete behavioral repertoires decreased. Cocaine also decreased, rather than facilitated, the incidence of D1CT transgene-induced compulsion-like behaviors such as repeated leaping and perseverance of any and all normal behaviors. The indistinguishable cocaine responses of D1CT and normal mice, as well as the masking (rather than potentiation) of D1CT mouse compulsion-like behaviors by cocaine, suggests that cortical-limbic induced compulsions are significantly different in their origin or circuitry from cocaine-induced stereotyped behaviors. Specifically, these data suggest that the motor circuits stimulated in compulsions represent only a subset of the parallel circuits stimulated by cocaine. These data are, thus, consistent with the hypothesis that topographically restricted subsets of parallel cortical-striatal-thalamic loops induce different types of compulsive behaviors.
Campbell
K M
KM
Department of Pharmacology, University of Minnesota, 3-249 Millard Hall, 435 Delaware St. S.E., Minneapolis MN 55455, USA.
McGrath
M J
MJ
Burton
F H
FH
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D002772:Cholera Toxin / Q000235:genetics; D003042:Cocaine / Q000494:pharmacology*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009771:Obsessive-Compulsive Disorder / Q000139:chemically induced / Q000503:physiopathology*; D017447:Receptors, Dopamine D1 / Q000235:genetics; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology; D019076:Transgenes
D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D018698:Glutamic Acid; D002772:Cholera Toxin; D003042:Cocaine