The Experts below are selected from a list of 96 Experts worldwide ranked by ideXlab platform
Randy J. Seeley - One of the best experts on this subject based on the ideXlab platform.
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Role for Dopamine-3 Receptor in the hyperphagia of an unanticipated high-fat meal in rats.
Pharmacology biochemistry and behavior, 2006Co-Authors: Jon F. Davis, John Andrews Mcquade, Deborah L. Drazen, Stephen C. Woods, Randy J. Seeley, Stephen C. BenoitAbstract:Behavioral studies have indicated that midbrain Dopamine projections arising in the ventral tegmental area and substantia nigra play a central role in integrating violations of expectancy in reward-related paradigms. The present study was designed to assess violations of dietary expectation and the role the Dopamine-3 Receptor plays in integrating reward-related food intake in violations of expectancy. Two groups of rats were conditioned to a meal-feeding schedule (3 h of access to food per day) in which they received either standard rodent chow or a preferable, high-fat diet. Animals either received the diet they had access to during the training period (no contrast) or the opposite diet (negative and positive contrast). As predicted, animals in the positive contrast condition were hyperphagic compared to no contrast animals. Animals in the negative contrast (high fat to chow) condition were hypophagic compared to no contrast animals. A Dopamine agonist specific to the Dopamine three Receptor, ((±)-7-Hydroxy-dipropylaminotetralin HBr) and the Dopamine-2 Receptor antagonist raclopride were administered in equimolar doses peripherally to assess the involvement of the Dopamine Receptor subtypes in the violation of expectancy food intake effects. 7-Hydroxy-dipropylaminotetralin HBr blocked the hyperphagia associated with positive contrast and did not disrupt intake in the negative contrast or no contrast paradigm. Raclopride was ineffective at disrupting food intake. These results support the hypothesis that the Dopamine-3 Receptor is involved in the hyperphagia of an unexpected high fat meal.
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High-fat diet induced adiposity in mice with targeted disruption of the Dopamine-3 Receptor gene.
Behavioural brain research, 2004Co-Authors: John Andrews Mcquade, Stephen C. Woods, Stephen C. Benoit, Randy J. SeeleyAbstract:Dopamine (DA) signaling has been implicated in the control of energy balance and ingestive behavior. In the present study, we sought to characterize body weight, body fat and food intake regulation in a mouse with a targeted disruption of the Dopamine-3 Receptor gene (Drd3). In the first set of experiments male and female wild-type and mutant (Drd3-/-) mice were given access to two different diets varying in fat content. Body weight, food intake, carcass analysis and plasma levels of leptin and insulin were measured. Male Drd3-/- mice have increased body weight and body fat when given access to high fat (HF) diet but not standard rodent chow. The female Drd3-/- mice did not demonstrate increased body weight when given access to either diet, but did have increased body fat on both diets. Plasma leptin and insulin levels reflected the increased adiposity demonstrated in each genotype and gender. These findings suggest the D3-R signaling is involved in the regulation of body weight and body fat when mice are given access to diets differing in palatability and fat content.
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Altered feeding responses in mice with targeted disruption of the Dopamine-3 Receptor gene.
Behavioral neuroscience, 2003Co-Authors: Stephen C. Benoit, John Andrews Mcquade, Stephen C. Woods, Deborah J. Clegg, Paul A. Rushing, Randy J. SeeleyAbstract:Dopamine signaling has been implicated in the control of food intake and body weight. In particular, Dopamine is important in the control of meal size and number and is thought to mediate the response to metabolic deprivation states. In the present experiments, the authors assessed the role of the Dopamine-3 Receptor (D 3 R) in the feeding responses to 2-deoxi-D-glucose, mercaptoacetate, and peripheral insulin. All 3 compounds increased food intake in wild-type mice, but the hyperphagic responses were blunted in D 3 R -/- mice. In other experiments, D 3 R / mice were hyperresponsive to the administration of amylin and leptin relative to wild-type mice. These results support the hypothesis that D 3 Rs; chronically inhibit the effects of adiposity hormone, thereby contributing to a net anabolic state.
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Ethanol consumption in mice with a targeted disruption of the Dopamine-3 Receptor gene.
Addiction biology, 2003Co-Authors: John Andrews Mcquade, Stephen C. Woods, Randy J. Seeley, Stephen C. BenoitAbstract:Considerable evidence suggests that the mesolimbic Dopaminergic system is an important substrate for the rewarding effects of ethanol consumption. Previous data have demonstrated that pharmacological agents that alter Dopamine signaling also influence the self-administration of ethanol. The present experiments were designed to assess the role of the Dopamine-3 Receptor (D3-R) on voluntary ethanol consumption in C57BL/6 mice. Mice with targeted disruption of the D3-R gene (D3-R - / -) were compared to wild-type controls in an ethanol intake paradigm. In Experiment 1, mice had 24-hour access to ethanol each day in a two-bottle choice paradigm for a period of 7 days per concentration. The concentrations tested were 3, 6, 10 and 15%. In Experiment 2, mice had 1 hour of access to ethanol each day in a two-bottle paradigm for a period of 7 days per concentration. The same concentrations in Experiment 1 were compared in Experiment 2. In Experiment 3 we sought to test the development of a conditioned taste aversion (CTA) after receiving an intraperitoneal (i.p.) injection of 2.0 glkg ethanol. In Experiment 4, blood ethanol levels where assessed following a 2.0 g/kg i.p. injection of ethanol. Experiment 5 assessed taste preference for saccharine and quinine in wild-type and D3-R - / - mice. Contrary to our predictions, both D3-R - / - and wild-types on a C57BL/6 background had similar intakes of ethanol, at all concentrations tested, in the 24-hour and 1-hour intake paradigms. Wild-type and D3-R - / - mice respond to injected ethanol similarly by developing a conditioned taste aversion. Metabolic analysis revealed mutant mice are slower in metabolizing a bolus injection of ethanol. Lastly, wild-type and D3-R - / - mice showed similar consumption to increasing concentration of both sweet and bitter tastes. These data suggest that deletion of the D3-R gene does not increase ethanol consumption above that found on the C57BL/6 genetic background. Furthermore, the D3-R - I - mice adequately learn a CTA to ethanol and do not have differing taste reactivity to saccharin or quinine. However, D3-R - / - mice do appear to have a slower rate of ethanol metabolism.
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7-OH-DPAT selectively reduces intake of both chow and high fat diets in different food intake regimens.
Pharmacology biochemistry and behavior, 2003Co-Authors: John-andrews M Mcquade, Stephen C. Woods, Stephen C. Benoit, Randy J. SeeleyAbstract:Mesolimbic Dopaminergic system activation correlates with ingestive behavior in numerous feeding regimens. DA release is enhanced by food intake following deprivation, amount of food consumed, and the palatability of the food consumed. The Dopamine-3 Receptor (D3-R) has a limited expression pattern that is restricted largely to the mesolimbic Dopaminergic system. The D3-R has been hypothesized to inhibit DA-mediated reward, locomotion and motivation. To test the potential for an inhibitory role of the D3-R on food intake, we administered the D3-R agonist 7-OH-DPAT (5, 10 and 50 microg/kg ip) to rats that had ad libitum access to standard rodent chow (3.41 kcal/gm, 0.51 kcal/gm from fat) or a preferable, high fat (HF) (4.4 kcal/gm, 1.71 kcal/gm from fat). In the second set of experiments we administered 7-OH-DPAT (10, 50 and 100 microg/kg) to rats that had access to chow or HF diet for only 3 h per day (meal fed). In the third set of experiments we administered 7-OH-DPAT (10 and 50 microg/kg) to rats that had access to chow or HF diet after a 21-h food restriction. The 10 and 50 microg/kg doses significantly, but equally reduced intake of chow and HF diet in animals that were ad libitum fed. In animals that were meal-fed the dose response was effectively shifted to the right and the 10 microg/kg dose was ineffective at reducing intake. The 50 and 100 microg/kg doses significantly but equally reduced intake of both diets. In animals that were 21-h restricted and had access to chow both the 10 and 50 microg/kg doses were ineffective at reducing intake. However, in animals that had access to HF diet, 7-OH-DPAT dose-dependently reduced intake. These results support a potential role for the D3-R in ingestive behavior particularly in situations that involve a significant learned component.
Stephen C. Benoit - One of the best experts on this subject based on the ideXlab platform.
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Role for Dopamine-3 Receptor in the hyperphagia of an unanticipated high-fat meal in rats.
Pharmacology biochemistry and behavior, 2006Co-Authors: Jon F. Davis, John Andrews Mcquade, Deborah L. Drazen, Stephen C. Woods, Randy J. Seeley, Stephen C. BenoitAbstract:Behavioral studies have indicated that midbrain Dopamine projections arising in the ventral tegmental area and substantia nigra play a central role in integrating violations of expectancy in reward-related paradigms. The present study was designed to assess violations of dietary expectation and the role the Dopamine-3 Receptor plays in integrating reward-related food intake in violations of expectancy. Two groups of rats were conditioned to a meal-feeding schedule (3 h of access to food per day) in which they received either standard rodent chow or a preferable, high-fat diet. Animals either received the diet they had access to during the training period (no contrast) or the opposite diet (negative and positive contrast). As predicted, animals in the positive contrast condition were hyperphagic compared to no contrast animals. Animals in the negative contrast (high fat to chow) condition were hypophagic compared to no contrast animals. A Dopamine agonist specific to the Dopamine three Receptor, ((±)-7-Hydroxy-dipropylaminotetralin HBr) and the Dopamine-2 Receptor antagonist raclopride were administered in equimolar doses peripherally to assess the involvement of the Dopamine Receptor subtypes in the violation of expectancy food intake effects. 7-Hydroxy-dipropylaminotetralin HBr blocked the hyperphagia associated with positive contrast and did not disrupt intake in the negative contrast or no contrast paradigm. Raclopride was ineffective at disrupting food intake. These results support the hypothesis that the Dopamine-3 Receptor is involved in the hyperphagia of an unexpected high fat meal.
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High-fat diet induced adiposity in mice with targeted disruption of the Dopamine-3 Receptor gene.
Behavioural brain research, 2004Co-Authors: John Andrews Mcquade, Stephen C. Woods, Stephen C. Benoit, Randy J. SeeleyAbstract:Dopamine (DA) signaling has been implicated in the control of energy balance and ingestive behavior. In the present study, we sought to characterize body weight, body fat and food intake regulation in a mouse with a targeted disruption of the Dopamine-3 Receptor gene (Drd3). In the first set of experiments male and female wild-type and mutant (Drd3-/-) mice were given access to two different diets varying in fat content. Body weight, food intake, carcass analysis and plasma levels of leptin and insulin were measured. Male Drd3-/- mice have increased body weight and body fat when given access to high fat (HF) diet but not standard rodent chow. The female Drd3-/- mice did not demonstrate increased body weight when given access to either diet, but did have increased body fat on both diets. Plasma leptin and insulin levels reflected the increased adiposity demonstrated in each genotype and gender. These findings suggest the D3-R signaling is involved in the regulation of body weight and body fat when mice are given access to diets differing in palatability and fat content.
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Altered feeding responses in mice with targeted disruption of the Dopamine-3 Receptor gene.
Behavioral neuroscience, 2003Co-Authors: Stephen C. Benoit, John Andrews Mcquade, Stephen C. Woods, Deborah J. Clegg, Paul A. Rushing, Randy J. SeeleyAbstract:Dopamine signaling has been implicated in the control of food intake and body weight. In particular, Dopamine is important in the control of meal size and number and is thought to mediate the response to metabolic deprivation states. In the present experiments, the authors assessed the role of the Dopamine-3 Receptor (D 3 R) in the feeding responses to 2-deoxi-D-glucose, mercaptoacetate, and peripheral insulin. All 3 compounds increased food intake in wild-type mice, but the hyperphagic responses were blunted in D 3 R -/- mice. In other experiments, D 3 R / mice were hyperresponsive to the administration of amylin and leptin relative to wild-type mice. These results support the hypothesis that D 3 Rs; chronically inhibit the effects of adiposity hormone, thereby contributing to a net anabolic state.
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Ethanol consumption in mice with a targeted disruption of the Dopamine-3 Receptor gene.
Addiction biology, 2003Co-Authors: John Andrews Mcquade, Stephen C. Woods, Randy J. Seeley, Stephen C. BenoitAbstract:Considerable evidence suggests that the mesolimbic Dopaminergic system is an important substrate for the rewarding effects of ethanol consumption. Previous data have demonstrated that pharmacological agents that alter Dopamine signaling also influence the self-administration of ethanol. The present experiments were designed to assess the role of the Dopamine-3 Receptor (D3-R) on voluntary ethanol consumption in C57BL/6 mice. Mice with targeted disruption of the D3-R gene (D3-R - / -) were compared to wild-type controls in an ethanol intake paradigm. In Experiment 1, mice had 24-hour access to ethanol each day in a two-bottle choice paradigm for a period of 7 days per concentration. The concentrations tested were 3, 6, 10 and 15%. In Experiment 2, mice had 1 hour of access to ethanol each day in a two-bottle paradigm for a period of 7 days per concentration. The same concentrations in Experiment 1 were compared in Experiment 2. In Experiment 3 we sought to test the development of a conditioned taste aversion (CTA) after receiving an intraperitoneal (i.p.) injection of 2.0 glkg ethanol. In Experiment 4, blood ethanol levels where assessed following a 2.0 g/kg i.p. injection of ethanol. Experiment 5 assessed taste preference for saccharine and quinine in wild-type and D3-R - / - mice. Contrary to our predictions, both D3-R - / - and wild-types on a C57BL/6 background had similar intakes of ethanol, at all concentrations tested, in the 24-hour and 1-hour intake paradigms. Wild-type and D3-R - / - mice respond to injected ethanol similarly by developing a conditioned taste aversion. Metabolic analysis revealed mutant mice are slower in metabolizing a bolus injection of ethanol. Lastly, wild-type and D3-R - / - mice showed similar consumption to increasing concentration of both sweet and bitter tastes. These data suggest that deletion of the D3-R gene does not increase ethanol consumption above that found on the C57BL/6 genetic background. Furthermore, the D3-R - I - mice adequately learn a CTA to ethanol and do not have differing taste reactivity to saccharin or quinine. However, D3-R - / - mice do appear to have a slower rate of ethanol metabolism.
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7-OH-DPAT selectively reduces intake of both chow and high fat diets in different food intake regimens.
Pharmacology biochemistry and behavior, 2003Co-Authors: John-andrews M Mcquade, Stephen C. Woods, Stephen C. Benoit, Randy J. SeeleyAbstract:Mesolimbic Dopaminergic system activation correlates with ingestive behavior in numerous feeding regimens. DA release is enhanced by food intake following deprivation, amount of food consumed, and the palatability of the food consumed. The Dopamine-3 Receptor (D3-R) has a limited expression pattern that is restricted largely to the mesolimbic Dopaminergic system. The D3-R has been hypothesized to inhibit DA-mediated reward, locomotion and motivation. To test the potential for an inhibitory role of the D3-R on food intake, we administered the D3-R agonist 7-OH-DPAT (5, 10 and 50 microg/kg ip) to rats that had ad libitum access to standard rodent chow (3.41 kcal/gm, 0.51 kcal/gm from fat) or a preferable, high fat (HF) (4.4 kcal/gm, 1.71 kcal/gm from fat). In the second set of experiments we administered 7-OH-DPAT (10, 50 and 100 microg/kg) to rats that had access to chow or HF diet for only 3 h per day (meal fed). In the third set of experiments we administered 7-OH-DPAT (10 and 50 microg/kg) to rats that had access to chow or HF diet after a 21-h food restriction. The 10 and 50 microg/kg doses significantly, but equally reduced intake of chow and HF diet in animals that were ad libitum fed. In animals that were meal-fed the dose response was effectively shifted to the right and the 10 microg/kg dose was ineffective at reducing intake. The 50 and 100 microg/kg doses significantly but equally reduced intake of both diets. In animals that were 21-h restricted and had access to chow both the 10 and 50 microg/kg doses were ineffective at reducing intake. However, in animals that had access to HF diet, 7-OH-DPAT dose-dependently reduced intake. These results support a potential role for the D3-R in ingestive behavior particularly in situations that involve a significant learned component.
Shaomeng Wang - One of the best experts on this subject based on the ideXlab platform.
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computational elucidation of the structural basis of ligand binding to the Dopamine 3 Receptor through docking and homology modeling
Journal of Medicinal Chemistry, 2006Co-Authors: Judith Varady Hobrath, Shaomeng WangAbstract:The Dopamine subtype 3 Receptor (D3) is a promising therapeutic target for the treatment of cocaine addiction, schizophrenia, Parkinson's disease, and other disorders, but little is known about the binding of ligands to D3 at the atomic level. In the present study, binding of 29 known ligands to the D3 Receptor was modeled computationally using four D3 Receptor models which were obtained from homology modeling. The predicted binding models were validated with experimental data from site-directed mutagenesis, structure−activity relationship studies, and affinity labeling studies. Docking scores calculated for these 29 ligands correlate reasonably well with the experimentally determined binding affinities. A pharmacophore model is proposed that describes the binding of ligands at a single D3 Receptor binding site and offers insights into the binding of structurally diverse D3 ligands to this Receptor.
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Design, synthesis, and evaluation of hexahydrobenz[f]isoquinolines as a novel class of Dopamine 3 Receptor ligands.
Bioorganic & medicinal chemistry letters, 2004Co-Authors: Jianyong Chen, Judith Varady, Beth Levant, Shaomeng WangAbstract:We previously identified hexahydrobenz[f]isoquinoline (4a) as a new class of Dopamine 3 Receptor (D(3)) ligand. Herein, we described the design, synthesis, and preliminary structure-activity relationships of new analogues of 4a as a novel class of D(3) ligands. Among these new analogues, compound 4 h is a potent D(3) ligand (K(i)=6.1 nM) and has a selectivity of 133-fold between D(3)- and D(2)-like Receptors, and of 163-fold between D(3)- and D(1)-like Receptors, respectively. Thus, compound 4 h represents a promising new lead compound for further design and optimization toward achieving highly potent and selective D(3) ligands.
Jim Van Os - One of the best experts on this subject based on the ideXlab platform.
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Antipsychotic-induced tardive dyskinesia and the Ser9Gly polymorphism in the DRD3 gene: a meta analysis.
Schizophrenia research, 2006Co-Authors: P Roberto Bakker, Peter N Van Harten, Jim Van OsAbstract:A polymorphic site in the gene encoding the Dopamine 3 Receptor (DRD3) resulting in a serine (Ser) into glycine (Gly) substitution has been shown to affect Dopamine binding affinity, and may contribute to individual differences in susceptibility to antipsychotic-induced tardive dyskinesia (TD). A Medline, EMBASE and PsychINFO search of literature published between 1976 and March 2005 yielded 11 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. The Gly allele increased the risk relative to the Ser allele (OR=1.17; 95% CI: 1.01-1.37) with evidence of publication bias. No significant genotype effects were apparent. TD may be associated with functional variation in the DRD3 allele. However, caution is required in interpreting this finding, as there is evidence of publication bias, genetic methodology has shortcomings, and the relation between antipsychotics, schizophrenia and TD is complex.
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Antipsychotic-induced tardive dyskinesia and the Ser9Gly polymorphism in the DRD3 gene: a meta analysis.
Schizophrenia Research, 2006Co-Authors: P Roberto Bakker, Peter N Van Harten, Jim Van OsAbstract:Abstract Background A polymorphic site in the gene encoding the Dopamine 3 Receptor (DRD3) resulting in a serine (Ser) into glycine (Gly) substitution has been shown to affect Dopamine binding affinity, and may contribute to individual differences in susceptibility to antipsychotic-induced tardive dyskinesia (TD). Methods A Medline, EMBASE and PsychINFO search of literature published between 1976 and March 2005 yielded 11 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. Results The Gly allele increased the risk relative to the Ser allele (OR = 1.17; 95% CI: 1.01–1.37) with evidence of publication bias. No significant genotype effects were apparent. Conclusions TD may be associated with functional variation in the DRD3 allele. However, caution is required in interpreting this finding, as there is evidence of publication bias, genetic methodology has shortcomings, and the relation between antipsychotics, schizophrenia and TD is complex.
Stephen C. Woods - One of the best experts on this subject based on the ideXlab platform.
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Role for Dopamine-3 Receptor in the hyperphagia of an unanticipated high-fat meal in rats.
Pharmacology biochemistry and behavior, 2006Co-Authors: Jon F. Davis, John Andrews Mcquade, Deborah L. Drazen, Stephen C. Woods, Randy J. Seeley, Stephen C. BenoitAbstract:Behavioral studies have indicated that midbrain Dopamine projections arising in the ventral tegmental area and substantia nigra play a central role in integrating violations of expectancy in reward-related paradigms. The present study was designed to assess violations of dietary expectation and the role the Dopamine-3 Receptor plays in integrating reward-related food intake in violations of expectancy. Two groups of rats were conditioned to a meal-feeding schedule (3 h of access to food per day) in which they received either standard rodent chow or a preferable, high-fat diet. Animals either received the diet they had access to during the training period (no contrast) or the opposite diet (negative and positive contrast). As predicted, animals in the positive contrast condition were hyperphagic compared to no contrast animals. Animals in the negative contrast (high fat to chow) condition were hypophagic compared to no contrast animals. A Dopamine agonist specific to the Dopamine three Receptor, ((±)-7-Hydroxy-dipropylaminotetralin HBr) and the Dopamine-2 Receptor antagonist raclopride were administered in equimolar doses peripherally to assess the involvement of the Dopamine Receptor subtypes in the violation of expectancy food intake effects. 7-Hydroxy-dipropylaminotetralin HBr blocked the hyperphagia associated with positive contrast and did not disrupt intake in the negative contrast or no contrast paradigm. Raclopride was ineffective at disrupting food intake. These results support the hypothesis that the Dopamine-3 Receptor is involved in the hyperphagia of an unexpected high fat meal.
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High-fat diet induced adiposity in mice with targeted disruption of the Dopamine-3 Receptor gene.
Behavioural brain research, 2004Co-Authors: John Andrews Mcquade, Stephen C. Woods, Stephen C. Benoit, Randy J. SeeleyAbstract:Dopamine (DA) signaling has been implicated in the control of energy balance and ingestive behavior. In the present study, we sought to characterize body weight, body fat and food intake regulation in a mouse with a targeted disruption of the Dopamine-3 Receptor gene (Drd3). In the first set of experiments male and female wild-type and mutant (Drd3-/-) mice were given access to two different diets varying in fat content. Body weight, food intake, carcass analysis and plasma levels of leptin and insulin were measured. Male Drd3-/- mice have increased body weight and body fat when given access to high fat (HF) diet but not standard rodent chow. The female Drd3-/- mice did not demonstrate increased body weight when given access to either diet, but did have increased body fat on both diets. Plasma leptin and insulin levels reflected the increased adiposity demonstrated in each genotype and gender. These findings suggest the D3-R signaling is involved in the regulation of body weight and body fat when mice are given access to diets differing in palatability and fat content.
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Altered feeding responses in mice with targeted disruption of the Dopamine-3 Receptor gene.
Behavioral neuroscience, 2003Co-Authors: Stephen C. Benoit, John Andrews Mcquade, Stephen C. Woods, Deborah J. Clegg, Paul A. Rushing, Randy J. SeeleyAbstract:Dopamine signaling has been implicated in the control of food intake and body weight. In particular, Dopamine is important in the control of meal size and number and is thought to mediate the response to metabolic deprivation states. In the present experiments, the authors assessed the role of the Dopamine-3 Receptor (D 3 R) in the feeding responses to 2-deoxi-D-glucose, mercaptoacetate, and peripheral insulin. All 3 compounds increased food intake in wild-type mice, but the hyperphagic responses were blunted in D 3 R -/- mice. In other experiments, D 3 R / mice were hyperresponsive to the administration of amylin and leptin relative to wild-type mice. These results support the hypothesis that D 3 Rs; chronically inhibit the effects of adiposity hormone, thereby contributing to a net anabolic state.
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Ethanol consumption in mice with a targeted disruption of the Dopamine-3 Receptor gene.
Addiction biology, 2003Co-Authors: John Andrews Mcquade, Stephen C. Woods, Randy J. Seeley, Stephen C. BenoitAbstract:Considerable evidence suggests that the mesolimbic Dopaminergic system is an important substrate for the rewarding effects of ethanol consumption. Previous data have demonstrated that pharmacological agents that alter Dopamine signaling also influence the self-administration of ethanol. The present experiments were designed to assess the role of the Dopamine-3 Receptor (D3-R) on voluntary ethanol consumption in C57BL/6 mice. Mice with targeted disruption of the D3-R gene (D3-R - / -) were compared to wild-type controls in an ethanol intake paradigm. In Experiment 1, mice had 24-hour access to ethanol each day in a two-bottle choice paradigm for a period of 7 days per concentration. The concentrations tested were 3, 6, 10 and 15%. In Experiment 2, mice had 1 hour of access to ethanol each day in a two-bottle paradigm for a period of 7 days per concentration. The same concentrations in Experiment 1 were compared in Experiment 2. In Experiment 3 we sought to test the development of a conditioned taste aversion (CTA) after receiving an intraperitoneal (i.p.) injection of 2.0 glkg ethanol. In Experiment 4, blood ethanol levels where assessed following a 2.0 g/kg i.p. injection of ethanol. Experiment 5 assessed taste preference for saccharine and quinine in wild-type and D3-R - / - mice. Contrary to our predictions, both D3-R - / - and wild-types on a C57BL/6 background had similar intakes of ethanol, at all concentrations tested, in the 24-hour and 1-hour intake paradigms. Wild-type and D3-R - / - mice respond to injected ethanol similarly by developing a conditioned taste aversion. Metabolic analysis revealed mutant mice are slower in metabolizing a bolus injection of ethanol. Lastly, wild-type and D3-R - / - mice showed similar consumption to increasing concentration of both sweet and bitter tastes. These data suggest that deletion of the D3-R gene does not increase ethanol consumption above that found on the C57BL/6 genetic background. Furthermore, the D3-R - I - mice adequately learn a CTA to ethanol and do not have differing taste reactivity to saccharin or quinine. However, D3-R - / - mice do appear to have a slower rate of ethanol metabolism.
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7-OH-DPAT selectively reduces intake of both chow and high fat diets in different food intake regimens.
Pharmacology biochemistry and behavior, 2003Co-Authors: John-andrews M Mcquade, Stephen C. Woods, Stephen C. Benoit, Randy J. SeeleyAbstract:Mesolimbic Dopaminergic system activation correlates with ingestive behavior in numerous feeding regimens. DA release is enhanced by food intake following deprivation, amount of food consumed, and the palatability of the food consumed. The Dopamine-3 Receptor (D3-R) has a limited expression pattern that is restricted largely to the mesolimbic Dopaminergic system. The D3-R has been hypothesized to inhibit DA-mediated reward, locomotion and motivation. To test the potential for an inhibitory role of the D3-R on food intake, we administered the D3-R agonist 7-OH-DPAT (5, 10 and 50 microg/kg ip) to rats that had ad libitum access to standard rodent chow (3.41 kcal/gm, 0.51 kcal/gm from fat) or a preferable, high fat (HF) (4.4 kcal/gm, 1.71 kcal/gm from fat). In the second set of experiments we administered 7-OH-DPAT (10, 50 and 100 microg/kg) to rats that had access to chow or HF diet for only 3 h per day (meal fed). In the third set of experiments we administered 7-OH-DPAT (10 and 50 microg/kg) to rats that had access to chow or HF diet after a 21-h food restriction. The 10 and 50 microg/kg doses significantly, but equally reduced intake of chow and HF diet in animals that were ad libitum fed. In animals that were meal-fed the dose response was effectively shifted to the right and the 10 microg/kg dose was ineffective at reducing intake. The 50 and 100 microg/kg doses significantly but equally reduced intake of both diets. In animals that were 21-h restricted and had access to chow both the 10 and 50 microg/kg doses were ineffective at reducing intake. However, in animals that had access to HF diet, 7-OH-DPAT dose-dependently reduced intake. These results support a potential role for the D3-R in ingestive behavior particularly in situations that involve a significant learned component.