Evidence suggests a critical role for dopamine in the reinforcing effects of cocaine in rats and primates. However, self-administration has been less often studied in the mouse species, and, to date, "knock-out" of individual dopamine-related genes in mice has not been reported to reduce the reinforcing effects of cocaine. We studied the dopamine D 1 receptor and cocaine self-administration in mice using a combination of gene-targeted mutation and pharmacological tools. Two cohorts with varied breeding and experimental histories were tested, and, in both cohorts, there was a significant decrease in the number of D 1 receptor knock-out mice that met criteria for acquisition of cocaine self-administration (
Sex differences in spatial navigation indicate that women may focus on positional, landmark cues whereas men favor Euclidean, directional cues. Some studies have investigated sex differences in proximal and distal cue use; however, sex differences in gradient (i.e., graded features) and pinpoint (i.e., single, defined) cue perception remain unexamined. In the current experiments, paired photographs were presented in which the 2nd photograph showed the same scene with cues removed (Experiment 1) or isolated (Experiment 2) from the 1st photograph. In Experiment 1, women showed less disruption of task performance than men showed following cue removal but were slowest after proximal pinpoint cue removal. Male performance was slowed by distal gradient and proximal pinpoint cue removal. In Experiment 2, women were faster than men at identifying isolated proximal and distal pinpoint cues and were more accurate at identifying isolated distal gradient and distal pinpoint cues. Better pinpoint cue perception and memory in women indicates one possible mechanism underlying female preference for landmark-based navigation strategies. Findings also show that whereas men may preferentially rely on distal gradient cues they are not better at perceiving those cues than are women.
Topiramate reduced ethanol preference in C57BL/6J mice, but this effect was primarily attributable to elevated water intake. Topiramate also reduced saccharin preference, likely through marginally significant increases in water intake. Increases in water intake and bidirectional effects of topiramate on ethanol dose complicate conclusions with regard to the effects of topiramate on ethanol reward.
These findings indicate that topiramate has no effect on ethanol's rewarding or conditioned rewarding effects as indexed by the place conditioning procedure. Thus, these studies raise the possibility that topiramate's efficacy in the treatment of alcoholism results from its impact on brain areas other than those that mediate ethanol's rewarding or conditioned rewarding effects. One alternative possibility is that topiramate decreases withdrawal-induced negative affective states that normally contribute to relapse.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.