Metabotropic glutamate receptor antagonists for treating tolerance and dependency

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(amended) A method or treating a mammalian subject suffering from tolerance or dependence, which method comprises administering to the subject a therapeutically effective amount of an antagonist of mGluR5.

(amended) A pharmaceutical composition comprising an antagonist of mGluR5and a therapeutic substance, wherein the use of the therapeutic substance in the absence of said antagonist could lead to tolerance of or dependence on the therapeutic substance.

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(amended) A method for screening a compound for use in the treatment of tolerance or dependence, comprising:

• (a) contacting a test compound with mGluR5 under the conditions that in the absence of the test compound would lead to activity of the said mGluR5;
• and
• determining whether the test compound antagonises mGluR5 activity.

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(new) A method of treating a subject with abstinence syndrome due to a substance selected from nicotine, an opiate, cocaine, an amphetamine, a benzodiazipine and ethanol,

• comprising administering a therapeutically effective amount of an antagonist of mGluR5 to said subject.

(new) A method of treating a subject with abstinence syndrome due to a substance selected from an opiate, cocaine, an amphetamine, and a benzodiazipine,

• comprising administering a therapeutically effective amount or an antagonist of mGluR5 to said subject.

(new) A method of treating a subject with abstinence syndrome due to ethanol,

• comprising administering a therapeutically effective amount of an antagonist of mGluR5 to said subject.

(new) A method of treating substance dependence in a mammalian subject in need thereof, where said substance is nicotine,

• comprising administering a therapeutically effective amount of of an antagonist of mGluR5 to said subject.

(new) A method of treating substance dependence in a mammalian subject in need thereof, where said substance is selected from an opiate, cocaine, an amphetamine, and a benzodiazipine,

• comprising administering a therapeutically effective amount of of an antagonist of mGluR5 to said subject.

(new) A method of treating substance dependence in a mammalian subject in need thereof, where said substance is ethanol,

• comprising administering a therapeutically effective amount of of an antagonist of mGluR5 to said subject.

(new) A method of treating tolerance to a therapeutic compound, where said compound is selected from opiates, amphetamines, and benzodiazipines,

• comprising administering a therapeutically effective amount of of an antagonist of mGluR5 to said subject

(new) A method of treating, in a mammalian subject, a condition selected from bulimia nervosa and anorexia, comprising administering a therapeutically effective amount of an antagonist of mGluR5 to said subject.

(new) A method of treating, in a mammalian subject, a condition selected from gambling dependence, sex dependence and obsessive compulsive disorder, comprising administering a therapeutically effective amount of an antagonist of mGluR5 to said subject.

(new) A pharmaceutical composition comprising pharmaceutically acceptable carrier, an antagonist of mGluR5, and a therapeutic substance selected from opiates, amphetamines, and benzodiazipines.