Table 1.
Animal studies.
| Author | Aim and Study Design | Numer of Subjects | Population | Lamotrigine Dose and Root |
Ketamine Dose and Root |
Tests and Measures | Outcome |
|---|---|---|---|---|---|---|---|
| Ostahadi et al. 2016 [40] | To investigate the involvement of NMDA receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) synthesis in possible antidepressant-like effect of lamotrigine in forced swimming test (FST) in mice. NMDA receptor antagonists and agonist were used for exploring the involvement of NMDA receptors in the antidepressant-like effect of lamotrigine. Placebo controlled Mean + SEM |
8 in a group | Male Naval Medical Research Institute (NMRI) mice | Lamotrigine 5 mg/kg intraperitoneally | Ketamine (1 mg/kg) intraperitoneally | FST | Co-administration of ketamine (1 mg/kg) and lamotrigine (3 mg/kg) resulted in an antidepressant-like effect in FST, NMDA receptor agonist reversed this antidepressant-like effect. |
| Reus et al. 2017 [41] | To investigate the synergistic interactions between fluoxetine, quetiapine and lamotrigine in combination with ketamine, Placebo controlled Mean ± SEM |
12 in a group, 8 groups | Male Wistar rats | (5.0 mg/kg) intraperitoneally |
(5.0 mg/kg) intraperitoneally |
FST OFT ST |
The levels of IL-1ß were reduced in the serum of rats receiving lamotrigine in combination with ketamine, compared to lamotrigine group No difference was observed in behavioral tests results Rats treated with fluoxetine and lamotrigine or with the combination of ketamine with fluoxetine or lamotrigine had a reduction in the lipid peroxidation, compared with group that received only ketamine. |
| Brody 2003 [42] | To assess the ability of lamotrigine to reduce the PPI– disruptive effects of ketamine and the dopaminergic agent amphetamine in two inbred mouse strains Placebo controlled Mean ± SEM. |
Not stated | two inbred mouse strains, C57BL/6J and 129SvPasIco. |
Lamotrigine (0,6.7, 13, or 27 mg/kg) or a combination of lamotrigine (27 mg/ kg) and either d-amphetamine or ketamine | ketamine (100 mg/kg) |
PPI | In the 129SvPasIco mice, lamotrigine reversed the ketamine-induced PPI deficit, without altering PPI in control mice. In C57BL/6J mice 27 mg/kg lamotrigine generally increased PPI in both control and ketamine-treated mice. |
| Cilia 2007 [43] | To investigate the effects of antipsychotics and lamotrigine upon ketamine-induced PPI deficits in rats. Placebo controlled Cross over design Mean ± SEM % PPI |
12 in a group | Male Sprague Dawley rats | lamotrigine (3–30 mg/kg p.o.; 60 min ptt) |
Ketamine (1–10 mg/kg s.c; 15 min ptt) | PPI | Ketamine significantly increased startle amplitude at all doses tested. Lamotrigine failed to significantly attenuate ketamine-induced PPI Deficits. It may be possible that the lack of effect of lamotrigine (3–10 mg/kg) in this study was due to strain and species differences. |
| Hunt et al. 2008 [44] | To examine if lamotrigine would disrupt ketamine-enhanced HFO Rats were pretreated with either saline or lamotrigine followed by injection of ketamine. A separate group received a unilateral intra-NAc infusion of lamotrigine followed by systemic injection of ketamine Placebo controlled Mean ± SEM |
32 | Wistar rats | Lamotrigine 0.1 mL/100 g rat weight intraperitoneal injection 3 doses 2 mg/kg, 6.7 mg/kg 20.1 mg/kg |
intraperitoneal injection of 25 mg/kg ketamine | HFO | Lamotrigine pretreatment had a significant effect on ketamine-induced behavioral activation Systemic injection of a high dose of lamotrigine (20.1 mg/kg) reduced the power and frequency of ketamine-enhanced HFO. Local infusion of lamotrigine into the NAc did not significantly affect ketamine-induced HFO. |
| Lee 2019 [45] | To find out if lamotrigine can reduce the motivation for ketamine use and ketamine seeking behavior in rats. Intravenous ketamine self-administration paradigm was used. Placebo controlled Mean ± SEM |
Not stated | Male Sprague-Dawley rats | lamotrigine orally 10 mg/kg 30 mg/kg |
intravenous ketamine (0.5 mg/kg/infusion) | IV ketamine self-administration paradigm | Lamotrigine 30 mg/kg attenuated the reinforcing efficacy of ketamine and educed ketamine craving and relapse risk |
IL-1ß = interleukine 1ß; NO-cGMP = Nitric oxide-cyclic guanosine monophosphate; PPI = prepulse inhibition; HFO = high frequency oscillations; FST;forced swimming test; OFT = open field test, ST = splash test; NMDA = N-Methyl-d-aspartate; SEM = standard error of the mean; SD = standard deviation.