However, an analysis of efficacy by drinking level revealed that the combination was superior to topiramate alone in heavy-drinking P rats, but was without effect in lighter-drinking P rats and Wistar rats. Both topiramate alone and the combination blocked the alcohol deprivation effect in both Wistar and P rats with the combination tending to produce a greater decrease than topiramate alone.
The combination of ondansetron and topiramate may be a promising treatment for preventing relapse and for treating alcohol dependence in heavy-, but not lighter-drinkers.”
“Subchronic administration to rodents of the N-methyl-d-aspartate non-competitive antagonist, phencyclidine (PCP), impairs
novel object recognition (NOR). Atypical antipsychotic drugs (APDs) reverse the effects of subchronic PCP on NOR. The effect of metabotropic glutamate(2/3) receptor (mGlu(2/3)) find more agonists upon NOR is unknown.
We tested the hypotheses that the mGlu(2/3) agonist, LY379268, by itself, or in combination
with APDs or pimavanserin, a 5-HT2A inverse agonist, would reverse the deficit in NOR induced by subchronic treatment with PCP (2 mg/kg, b.i.d., for 7 days).
The mGlu(2/3) agonist LY379268 (1 or 3 mg/kg) did not attenuate PD-1/PD-L1 Inhibitor 3 manufacturer the PCP-induced NOR deficit. However, together with sub-effective dose of the atypical APDs, clozapine (0.1 mg/kg) or lurasidone (0.03 mg/kg), but not the typical APD, haloperidol (0.1 mg/kg), or pimavanserin (3 mg/kg), LY379268, 1 mg/kg, significantly reversed the PCP-induced NOR deficit. Moreover, the effect of clozapine was blocked by the mGlu(2/3) antagonist, LY341495 (1 mg/kg).
These results indicate that mGlu(2/3) agonism can potentiate the ability of atypical, but not typical APDs, to ameliorate the effect of subchronic PCP on NOR, that mGlu(2/3) agonism may contribute to the ability of atypical APDs these to acutely reverse the effect of subchronic PCP on NOR, but that by itself, mGlu(2/3) agonism, is ineffective in this model of cognitive impairment in schizophrenia. These results suggest that mGlu(2/3) receptor agonism should be investigated as an adjunctive treatment of cognitive impairment in schizophrenia
rather than as monotherapy, which may be effective for control of psychosis, but not for cognitive impairment.”
“The effects of d-cycloserine (DCS) in animal models of anxiety disorders and addiction indicate a role for N-methyl d-aspartate (NMDA) receptors in extinction learning. Exposure/response prevention treatments for anxiety disorders in humans are enhanced by DCS, suggesting a promising co-therapy regime, mediated by NMDA receptors. Exposure/response prevention may also be effective in problematic drinkers, and DCS might enhance habituation to cues in these individuals. Since heavy drinkers show ostensible conditioned responses to alcohol cues, habituation following exposure/response prevention should be evident in these drinkers, with DCS enhancing this effect.