5 ht receptor mediated neurogenesis

Abstract

The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis. The disclosure includes compositions and methods based on use of a 5HTR agent, optionally in combination with one or more other neurogenic agents, to stimulate or activate the formation of new nerve cells.

1 . A method of improving the efficacy of a 5HTR agent in treating a subject or patient with a psychiatric condition comprising administering the 5HTR agent with a second agent to the subject or patient, wherein the efficacy of the 5HTR agent in combination is improved relative to the efficacy of the 5HTR agent used individually. 
   
   
       2 . The method of  claim 1 , wherein the combination is administered at a dosage that would be sub-therapeutic for either agent individually. 
   
   
       3 . The method of  claim 1 , wherein the combination is administered less frequently relative to the use of either agent individually. 
   
   
       4 . The method of  claim 1 , wherein the psychiatric condition is a mood disorder. 
   
   
       5 . The method of  claim 4 , wherein the mood disorder is selected from the group consisting of depression and anxiety. 
   
   
       6 . The method of  claim 1 , wherein the 5HTR agent is selected from the group consisting of a 5HT1a agonist, a 5HT3 antagonist, and a 5HT4 agonist. 
   
   
       7 . The method of  claim 6 , wherein the 5HT1a agonist is selected from the group consisting of buspirone, gepirone, tandospirone, and ipsapirone. 
   
   
       8 . The method of  claim 6 , wherein the 5HT3 antagonist is selected from the group consisting of azasetron, granisetron, and ondansetron. 
   
   
       9 . The method of  claim 6 , wherein the 5HT4 agonist is selected from the group consisting of mosapride and cisapride. 
   
   
       10 . The method of  claim 1 , wherein the second agent is selected from the group consisting of a modulator of a melatonin receptor, a GABA modulator, an α1 adrenergic receptor modulator, an opioid agent, a psychostimulant, a norepinephrine and dopamine reuptake inhibitor, and folic acid or a derivative thereof. 
   
   
       11 . The method of  claim 10 , wherein the modulator of a melatonin receptor is selected from the group consisting of melatonin and ramelteon. 
   
   
       12 . The method of  claim 10 , wherein the GABA modulator is selected from the group consisting of baclofen and gabapentin. 
   
   
       13 . The method of  claim 10 , wherein the α1 adrenergic receptor modulator is modafinil. 
   
   
       14 . The method of  claim 10 , wherein the opioid agent is selected from the group consisting of naltrexone and naloxone. 
   
   
       15 . The method of  claim 10 , wherein the psychostimulant is methylphenidate. 
   
   
       16 . The method of  claim 10 , wherein the norepinephrine and dopamine reuptake inhibitor is buproprion. 
   
   
       17 . The method of  claim 10 , wherein the folic acid derivative is methyl folate. 
   
   
       18 . A method of improving efficacy of a 5HTR agent in treating a psychiatric condition in a subject comprising administering to the subject the 5HTR agent in combination with an agent that inhibits, reduces, or prevents astrogenesis, thereby improving the efficacy of the 5HTR agent. 
   
   
       19 . The method of  claim 18 , wherein the psychiatric condition is a mood disorder. 
   
   
       20 . The method of  claim 19 , wherein the mood disorder is selected from the group consisting of depression and anxiety. 
   
   
       21 . The method of  claim 18 , wherein the combination is administered at a dosage that would be sub-therapeutic for either agent individually. 
   
   
       22 . The method of  claim 18 , wherein the 5HTR agent is selected from the group consisting of a 5HT1a agonist, a 5HT3 antagonist, and a 5HT4 agonist. 
   
   
       23 . The method of  claim 18 , wherein the second agent is selected from the group consisting of a modulator of a melatonin receptor, a GABA modulator, an α1 adrenergic receptor modulator, an opioid agent, a psychostimulant, a norepinephrine and dopamine reuptake inhibitor, and folic acid or a derivative thereof. 
   
   
       24 . A method of increasing the number of neurons in a cell population or tissue comprising, contacting the cell population or tissue with a 5HTR agent and a second agent that reduces or suppresses the amount or level of astrogenesis, thereby increasing number of neurons in the cell population or tissue. 
   
   
       25 . The method of  claim 24 , wherein expression of TUJ-1 is increased in the cell population or tissue. 
   
   
       26 . The method of  claim 24 , wherein expression of GFAP is decreased in the cell population or tissue. 
   
   
       27 . The method of  claim 24 , wherein the 5HTR agent is selected from the group consisting of a 5HT1a agonist, a 5HT3 antagonist, and a 5HT4 agonist. 
   
   
       28 . The method of  claim 24 , wherein the second agent is selected from the group consisting of a modulator of a melatonin receptor, a GABA modulator, an α1 adrenergic receptor modulator, an opioid agent, a psychostimulant, a norepinephrine and dopamine reuptake inhibitor, and folic acid or a derivative thereof. 
   
   
       29 . A method of decreasing the level of astrogenesis in a cell or cell population, the method comprising contacting the cell or cell population with an astrogenic 5HTR agent and a second agent that reduces or suppresses the amount or level of astrogenesis caused by the 5HTR agent, thereby decreasing the level of astrogenesis in the cell or cell population. 
   
   
       30 . The method of  claim 29 , wherein the 5HTR agent is selected from the group consisting of a 5HT1a agonist, a 5HT3 antagonist, and a 5HT4 agonist. 
   
   
       31 . The method of  claim 29 , wherein the second agent is selected from the group consisting of a modulator of a melatonin receptor, a GABA modulator, an α1 adrenergic receptor modulator, an opioid agent, a psychostimulant, a norepinephrine and dopamine reuptake inhibitor, and folic acid or a derivative thereof.