Neurotensin receptor type 1 (NTS1) is known to mediate a variety of biological functions of neurotensin (NT) in the central nervous system. In this study, we found that NTS1 null mice displayed decreased sensitivity to the ataxic effect of ethanol on the rotarod and increased ethanol consumption when given free choice between ethanol and tap water containing bottles. Interestingly, the administration of NT69L, a brain-permeable NT analog, increased ethanol sensitivity in wild-type littermates but had no such effect in NTS1 null mice, suggesting that NTS1 contributes to NT-mediated ethanol intoxication. Furthermore, the daily treatment of NT69L, for 4 consecutive days, significantly reduced alcohol preference and consumption in wild-type littermates but had no such effects in NTS1 null mice in a two-bottle drinking experiment. Our study provides evidence for one possible pharmacological role of NT69L in which it increases sensitivity to the ataxic effect, and decreases voluntary consumption, of ethanol. Our study also demonstrates NTS1-mediated behavioral effects of NT69L. Therefore, our findings will be useful for understanding some aspects of alcoholism as well as to develop novel pharmacological therapeutic options for humans.
Background-Neurotensin receptors (NTS) regulate a variety of the biological functions of neurotensin (NT) in the central nervous system. Although NT and NT receptor type 1 (NTS1) are implicated in some of the behavioral effects of ethanol, the functional roles of NT receptor type 2 (NTS2) in ethanol intoxication and consumption remain unknown. Here we investigated behavioral effects mediated by NTS2 in response to ethanol, which are implicated in ethanol consumption and preference, using NTS2 null mice.
To date, only modest numbers of pediatric studies using magnetic resonance imaging have been conducted. Most of these studies have small sample sizes and heterogeneous subject groups. These studies have provided important information regarding the underlying neuro-circuitry and pathophysiology of these complex and disabling disorders, however.
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