Forskolin & inositol: increased motivation via D2 receptor proliferation in striatum?

[shibireru]

Forskolin & inositol: increased motivation via D2 receptor proliferation in striatum?

Is it reasonable to assume that either of both of these substances would have such an effect?

And is there any reason to assume that these substances could increase D2 receptor density in other brain regions as well?


Forskolin:

http://www.ncbi.nlm.nih.gov/pubmed/9353595

Molecular mechanisms underlying forskolin-mediated up-regulation of human dopamine D2L receptors.

Abstract:
1. Human dopamine (DA) D2long (hD2L) receptors, expressed by Ltk- cells, can be up-regulated by treating the cells with forskolin for 16 hr (Johansson and Westlind-Danielsson, 1994). We have examined some of the molecular mechanisms underlying this forskolin-mediated up-regulation. 2. Forskolin (100 microM, 16 hr), but not 1,9-dideoxyforskolin, a forskolin analogue that is unable to activate adenylyl cyclase and raise intracellular cAMP concentrations, up-regulates the hD2L receptor population by 43%. The implication of a cAMP-dependent increase in the receptor up-regulation was further substantiated by treating the cells with 8-bromo-cAMP or prostaglandin E1 (PGE1). The forskolin-mediated rise in receptor number was blocked by cycloheximide or an antisense phosphorothioate oligodeoxynucleotide (ODN) directed toward the hD2L mRNA. KT5720, a specific protein kinase A (PKA) inhibitor, completely blocked the receptor rise, whereas pertussis toxin (PTX) attenuated the increase considerably. Forskolin also produced an increase in the level of the DA hD2short (hD2S) receptor expressed by Ltk- cells. This increase was 2.5-fold higher than that found for the hD2L receptor. 3. The forskolin-mediated hD2L receptor rise is dependent on de novo protein synthesis, a rise in cAMP levels, PKA activation, and, at least partially, PTX-sensitive G proteins. 4. Long-term increases in intracellular cAMP levels may change the sensitivity of a DA receptor expressing cell to DA by increasing D2 receptor density through enhanced cAMP-dependent transcription.

http://cat.inist.fr/?aModele=afficheN&cpsidt=2825818

Dopamine D2 receptor upregulation in rat neostriatum following in vivo infusion of forskolin

Abstract:
INTRACEREBROVENTRICULAR (i.c.v.) forskolin infusion for 5 days resulted in a concentration-dependent increase in rat striatal dopamine (DA) D2 receptors measured with [3Hjraclopride. In animals given 50 nmol/h forskolin, the highest concentration used, raclopride-mediated suppression of spontaneous locomotor activity was attenuated, and (±)-7-hydroxy-dipropyl-amino-tetralin HBr (7-OH-DPAT)-mediated inhibition of striatal DA synthesis, as estimated by the accumulation of DOPA following inhibition of cerebral decarboxylase, was enhanced. These data suggest that the DA D2 receptor increase comprises receptors localized both post- and presynaptically. The density of striatal DA D1 receptors was also changed with the forskolin treatment, in a concentration-dependent fashion, but in the opposite direction to DA D2 receptors. These findings suggest that striatal DA receptor sensitivity can be changed by manipulation at the second messenger level (e.g. independent of direct neurotransmitter-receptor interactions) in vivo.

Inositol:

http://cat.inist.fr/?aModele=afficheN&cpsidt=942196

Chronic inositol increases striatal D2 receptors but does not modify dexamphetamine-induced motor behavior. Relevance to obsessive-compulsive disorder

Abstract:
A large body of evidence suggests that the neuropathology of obsessive-compulsive disorder (OCD) lies in the complex neurotransmitter network of the cortico-striatal-thalamo-cortical (CSTC) circuit, where dopamine (DA), serotonin (5HT), glutamate (Glu), and gamma-amino butyric acid (GABA) dysfunction have been implicated in the disorder. Chronic inositol has been found to be effective in specific disorders that respond to selective serotonin reuptake inhibitors (SSRIs), including OCD, panic, and depression. This selective mechanism of action is obscure. Since nigro-striatal DA tracts are subject to 5HT2 heteroreceptor regulation, one possible mechanism of inositol in OCD may involve its effects on inositol-dependent receptors, especially the 5HT2 receptor, and a resulting effect on DA pathways in the striatum. In order to investigate this possible interaction, we exposed guinea pigs to oral inositol (1.2 g/kg) for 12 weeks. Subsequently, effects on locomotor behavior (LB) and stereotype behavior (SB), together with possible changes to striatal 5HT2 and D2 receptor function, were determined. In addition, the effects of chronic inositol on dexamphetamine (DEX)-induced motor behavior were evaluated. Acute DEX (3 mg/kg, ip) induced a significant increase in both SB and LB, while chronic inositol alone did not modify LA or SB. The behavioral response to DEX was also not modified by chronic inositol pretreatment. However, chronic inositol induced a significant increase in striatal D2 receptor density (Borax) with a slight, albeit insignificant, increase in 5HT2 receptor density. This suggests that D2 receptor upregulation may play an important role in the behavioral effects of inositol although the role of the 5HT2 receptor in this response is questionable.

 

[Coolio]

I'd like to try this combo...

 

[Temeraroius]

Seems interesting, but when I first glanced at the thread I swore I read "foreskin" not "forskolin"

 

[shibireru]

Seems interesting, but when I first glanced at the thread I swore I read "foreskin" not "forskolin"

Yeah, me too. And when I saw your username I thought it was "temerarious"..... but it's not.

/Sucky time for a typo, eh?

 

[Tsukasa]

I always though inositol (a b-vitamin) only had affects on 5-HT, but this is definately interesting since i'm doing research with this.

 

[keeponkeepnon]

Sorry to resurrect an old thread but I came across the same study recently while researching Inositol for OCD. I wonder if someone could explain how an "a significant increase in striatal D2 receptor density (Borax) ie upregulation ?" Would translate to someone who has ADD and uses D-amphetamine ? Is it essentially saying there is no impact on theraputic effects with regard to cognition but reduction of OCD symptoms because of the upregulation in a distinctly different area of the brain than the prefrontal cortex ?