Gabapentin, Synaptogenesis and Learning?

[Cotcha Yankinov]

I was hoping someone could give me an opinion on whether or not Gabapentin (with its anti thrombospondin effects) would be thought to be harmful to learning. I believe one study advised not to use Gabapentin in models of neuronal injury and the two examples they gave were stroke and traumatic brain injury.

Will Gabapentin decrease my capacity to learn by any significant amount or are the mechanisms of learning separate from synaptogenesis (long term potentiation??)? Or alternatively, does Gabapentin not have enough of an effect on synaptogenesis related to learning to make a noticeable difference?

 

[serotonin2A]

I was hoping someone could give me an opinion on whether or not Gabapentin (with its anti thrombospondin effects) would be thought to be harmful to learning. I believe one study advised not to use Gabapentin in models of neuronal injury and the two examples they gave were stroke and traumatic brain injury.

Will Gabapentin decrease my capacity to learn by any significant amount or are the mechanisms of learning separate from synaptogenesis (long term potentiation??)? Or alternatively, does Gabapentin not have enough of an effect on synaptogenesis related to learning to make a noticeable difference?

The effects you are talking about have been shown in mice, not humans. It isn't known if they happen in humans, or how dose-dependent the effect is. But clearly people taking gabapentin are capable of synaptogenesis. If you are taking gabapentin then you can conduct a simple experiment: read a book. If you can keep track of the plot, then your brain is capable of synaptogenesis.

If your brain stopped making new synapses, or even just slowed down, then it would be very obvious to you. You would feel noticibly impaired.

 

[Solipsis]

Stopping creation of new synapses is an extreme.

The question was if cognitive capacities would be decreased, not obliterated, right?

I recall from an old Bluelighter that he did find taking gabapentinoids chronically to have negative impact on cognition and learning, and having over a year of experience with daily prescribed Lyrica myself I would confirm that 'dumbing down' unfortunately. It is one of the downsides yea IMO, although - especially if the withdrawals turn out to be reasonable - I am generally pretty impressed by VDCC blockers altogether (experience with pregabalin, gabapentin and phenibut).

 

[Cotcha Yankinov]

Are there fundamental processes in the brain that require a base level of synaptogenesis that may be interrupted by Gabapentin? I was wondering if Gabapentin (via reducing synaptogenesis a small amount) might bring about neurodegenerative disease, I suppose a parallel is concerning this MDMA study, it was asking whether or not MDMA users were going to have increased neurodegenerative disease because of a small loss serotonin essentially being revealed in old age as brain cells are naturally lost.

Is synaptogenesis important at 20 years old for dopamine or is dopamine generally done forming synapse wise? Just wondering if decreasing synaptogenesis might increase Parkinson's related disease likelihood, or essentially further pathology in someone who will already develop symptoms with age.

 

[serotonin2A]

Are there fundamental processes in the brain that require a base level of synaptogenesis that may be interrupted by Gabapentin? I was wondering if Gabapentin (via reducing synaptogenesis a small amount) might bring about neurodegenerative disease, I suppose a parallel is concerning this MDMA study, it was asking whether or not MDMA users were going to have increased neurodegenerative disease because of a small loss serotonin essentially being revealed in old age as brain cells are naturally lost.

Is synaptogenesis important at 20 years old for dopamine or is dopamine generally done forming synapse wise? Just wondering if decreasing synaptogenesis might increase Parkinson's related disease likelihood, or essentially further pathology in someone who will already develop symptoms with age.

^Solopsis: The OP indirectly referenced an article suggesting that gabapentin inhibits synaptogenesis. So my assumption is that he is asking whether it produces the same effects in humans. The implications of such an effect are not necessarily very mild.

http://www.ncbi.nlm.nih.gov/pubmed/19818485

^CY: Parkinson's disease isn't an illness of synapse formation. It is caused by a loss of dopamine neurons. A reduction of synaptogenesis and neurodegeneration are completely different processes. The worry with MDMA toxicity is that there would be functional compensation for axon/terminal loss that would diminish over time as serotonin levels decline. You have to keep in mind that reductions in synaptogenesus or even synapse loss doesn't imply axon loss -- the projection still exists, but it just may not communicate as much with a particular cell.

 

[Cotcha Yankinov]

This papers idea that Gabapentins MOA might be via inhibiting synaptogenesis, is it mostly concerning the peripheral nerves where upon nerve injury there might be some aberrant synaptogenesis with the astrocytosis?

Would you say Gabapentin's main MOA is more likely modulation of synaptic firing via calcium channels and not modulating synaptogenesis?

I was wondering if reduced synaptogenesis (chronically) would be expected to exacerbate any sort of neuropathy or neurodegenerative disease where there's already not enough transmission. I mean it seems all fine and well that preventing the aberrant synaptogenesis might prevent the pain issues but wouldn't it ultimately weaken the nerves?

Or is all this inhibition of synaptogenesis stuff BS and Gabapentin just works mainly by modulating synaptic transmission?