Here's a bad consequence re: ibuprufen:

I can email the full article if desired.

Deficits in spatial learning and synaptic plasticity induced by the rapid and competitive broad-spectrum cyclooxygenase inhibitor ibuprofen are reversed by increasing endogenous brain-derived neurotrophic factor

* Kendra N. Shaw,
* Sean Commins and
* Shane M. O'Mara

Cyclooxygenase (COX), which is present in two isoforms (COX1 and 2), synthesizes prostaglandins from arachidonic acid; it plays a crucial role in inflammation in both central and peripheral tissues.

Here, we describe its role in synaptic plasticity and spatial learning in vivo via an effect on brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2; both measured by Elisa).

We found that broad-spectrum COX inhibition (BSCI) inhibits the induction of long-term potentiation (LTP; the major contemporary model of synaptic plasticity), and causes substantial and sustained deficits in spatial learning in the watermaze.

Increases in BDNF and PGE2 following spatial learning and LTP were also blocked. Importantly, 4 days of prior exercise in a running wheel increased endogenous BDNF levels sufficiently to reverse the BSCI of LTP and spatial learning, and restored a parallel increase in LTP and learning-related BDNF and PGE2. In control experiments, we found that BSCI had no effect on baseline synaptic transmission or on the nonhippocampal visible-platform task; there was no evidence of gastric ulceration from BSCI.

COX2 is inhibited by glucorticoids; there was no difference in blood corticosterone levels as measured by radioimmunoassay in any condition.

Thus, COX plays a previously undescribed, permissive role in synaptic plasticity and spatial learning via a BDNF-associated mechanism.

http://www.blackwell-synergy.com/doi...8.2003.02643.x

....The slow, time-dependent, reversible COX inhibitor indomethacin (Dannhardt & Kiefer, 2001) does not, however, block the induction of LTP (Williams & Bliss, 1989; Yamagata et al., 1993); it is possible that the particular pharmacological profile of indomethacin accounts for this lack of an inhibitory effect on LTP. To date, there has been no systematic evaluation of the effects of the many other COX-inhibiting drugs on synaptic plasticity.....

....Apart from these studies, there appear to be few data available on the effects of COX inhibition or activation on synaptic plasticity or learning; the NMDA-receptor-related regulation of COX activity is suggestive of a role for COX in synaptic plasticity (see also Miettinen et al., 1997; who have shown that spreading depression, another form of neuroplasticity, also induces COX-2 activation in cortical neurons)......


....We therefore have provided the first evidence that COX is involved in BDNF expression, LTP and spatial learning; we have provided the first evidence that exercise, which increases levels of endogenous BDNF, also reverses ibuprofen-induced deficit in LTP and spatial learning. We have shown for the first time that PGE2 plays an important regulatory role in synaptic plasticity and learning. We have also confirmed here our previous data (Gooney et al., 2002) showing that both spatial learning and LTP are associated with an increase in BDNF. ....

...Salvemini et al. (1993) found that COX2 is modulated by nitric oxide (NO), a gaseous molecule that plays a role in synaptic plasticity and cellular death. In view of the many regulatory signals involved in COX2 activity and its localization in spines, Kauffman et al. (1996) suggest that COX2 may generate a diffusible signal as a function of the activity at specific synapses. C-fos is rapidly induced by hippocampal NMDA activation and blocked by COX inhibition (Lerea & McNamara, 1993). Because c-fos activity must involve events in the nucleus, it suggests a COX-dependent signal linking receptor activation and gene expression.....