Effects of the anticonvulsant lacosamide compared to valproate and lamotrigine on cocaine-enhanced reward in rats

Abstract Some drugs developed as anticonvulsants (notably, valproate and lamotrigine) have therapeutic effects in bipolar and related disorders. Lacosamide, a recently approved anticonvulsant, has unique effects on sodium channels that may play a role in producing the mood-stabilizing effects of anticonvulsant drugs. We tested whether lacosamide would have effects similar to or different from valproate and lamotrigine in a model of reward and elevated mood. The intracranial self-stimulation (ICSS) test is sensitive to the function of brain reward systems. Changes in ICSS may model aspects of disorders characterized by abnormalities of reward and motivation. Cocaine elevates mood, and reduction of cocaine-induced facilitation of ICSS has been used to predict antimanic-like or mood stabilizing effects of drugs. We tested lacosamide, lamotrigine, and valproate in the rat ICSS test alone or in the presence of cocaine. A high dose of lacosamide (30 mg/kg) significantly elevated ICSS thresholds, indicating that it reduced the rewarding impact of medial forebrain bundle stimulation. Lower doses (3–10 mg/kg) did not alter ICSS, but blocked the cocaine-induced lowering of ICSS thresholds. The highest doses of valproate (300 mg/kg) and lamotrigine (30 mg/kg) also elevated ICSS thresholds, and only these high doses significantly lowered cocaine-induced effects. Of the drugs tested, only lacosamide significantly attenuated the reward-facilitating effects of cocaine at doses that had no effects on ICSS response in the absence of cocaine. Abnormalities of mood and reward are common in psychiatric disorders, and these results suggest that lacosamide deserves further study in models of these disorders.