Table 2.
Implications of the hippocampal endogenous opioid system on excitability, epilepsy, and neuroprotective potentials.
| Implications | Model | References |
|---|---|---|
| Stimulation of hippocampal granule cells inhibits perforant path terminals potentially via presynaptic KOPr on perforant path axons | Guinea pig, rodents | Wagner et al., 1993; Drake et al., 1994; Salin et al., 1995 |
| Stimulation of mossy fibers inhibits neighboring mossy fibers via Dyn | Guinea pig | Weisskopf et al., 1993 |
| Dyn exerts anticonvulsant effects | Various rodent models | Tortella et al., 1986, 1989, 1990; Przewlocka et al., 1995; Solbrig et al., 2006; Loacker et al., 2007 |
| Antiepileptogenic effects of Dyn is mediated via the KOPr | Rodent kainic acid model | Loacker et al., 2007 |
| Low pDyn levels due to mutations in the promoter regions result in increased vulnerability for epilepsy | Human epilepsy patients | Stogmann et al., 2002; Gambardella et al., 2003 |
| KOPr activation in periods of low Dyn suppresses seizures | Various rodent models | Tortella, 1988; Takahashi et al., 1990; Solbrig et al., 2006; Loacker et al., 2007 |
| KOPr activation during epileptogenesis increases neuronal survival | Rodent kainic acid model | Schunk et al., 2011 |
| Pharmacological MOPr or DOPr activation has disinhibititory effects and facilitats synaptic plasticity/seizure susceptibility | Rodents | Neumaier et al., 1988; Cohen et al., 1992; Lupica, 1995 |
| DOPr inhibition prevents, and DOPr-activation facilitates self-sustained status epilepticus | Performant path stimulation in rats | Mazarati et al., 1999 |
| Subcutaneous DOPr agonist administration produce convulsions | Rodent kindling model | Broom et al., 2002; Jutkiewicz et al., 2006 |
| DOPr agonists produce moderate convulsions | Non-human primate kindling model | Negus et al., 1998; Danielsson et al., 2006 |
| Intrahippocampal β-endorphin injections result in generalized convulsions, administration into the ventricle strongly reduces this effect | Rodent kindling model | Cain et al., 1990 |
| Neuroprotection of DOPr activation | Hypoxia/ischemia, glutamate-induced excitotoxic injury and oxidative stress models | Mayfield and D'Alecy, 1994; Zhang et al., 2000; Narita et al., 2006; Yang et al., 2009 |