Morphine State-Dependent Learning Sensitization and Interaction with Nitric Oxide

Abstract

In the present study, the effects of nitric oxide (NO) precursor L-arginine and L-NAME, a potent inhibitor of NO synthase (NOS), on the expression of sensitization of morphine were investigated. Pre-training administration of morphine (5 mg/kg) impaired memory retrieval compared to pre-training saline-treated animals. Amnesia due to pre-training morphine (5 mg/kg) was restored by pre-test morphine (5 mg/kg).The retrieval impairment was also inhibited in mice which had received once-daily injections of morphine (20 and 30 mg/kg, s.c.) for 3 days, followed by 5 days of no drug treatment before training (in order to induce morphine sensitization). Administration of L-arginine (60 mg/kg/day – 3 days) or L-NAME (20 mg/kg/day – 3 days) before training did not alter morphine state dependency. During acquisition of sensitization, administration of L-arginine (60 mg/kg) 20 min before morphine (10 mg/kg/day, for 3 days) increased, while injection of L-NAME (20 mg/kg) 20 min before morphine (30 mg/kg/day, for 3 days) decreased morphine state dependency. It is concluded that NO is involved in the morphine-induced sensitization.

Involvement of neuronal nitric oxide synthase in cross-sensitization between chronic unpredictable stress and ethanol in adolescent and adult mice

“…In fact, adolescents show higher, similar, or lower ACTH and corticosterone responses, depending on the type of stressor (Romeo, Patel, Pham, & So, 2016). nNOS inhibition by 7NI reduced both ethanol sensitization and cross-sensitization with stress, which is in agreement with studies showing that inhibition of nNOS blocks cocaine-induced sensitization and cross-sensitization between cocaine and methamphetamine (Itzhak, 1997), methamphetamine sensitization (Inoue, Arai, Shibata, & Watanabe, 1996), and morphine sensitization (Zarrindast, Askari, Khalilzadeh, & Nouraei, 2006). The NOS system appears to have an important role in behavioral sensitization, in drugs' rewarding effects, and other aspects of addiction.…”

Interactions between morphine and nitric oxide in various organs

“…Endogenous NO may play a role in the modulation of the dopaminergic effects elicited by morphine. The administration of L-arginine or L-NAME before training did not alter morphine state-dependent learning; during the acquisition of sensitization, L-arginine administered before morphine increased, while L-NAME administered before morphine decreased morphine-state dependency, suggesting that NO is involved in the morphine-induced learning sensitization [30]. Whether the controversial effects of endogenous NO, that it either enhances or inhibits morphine actions, are associated with low and high concentrations of NO formed by cNOS and iNOS, respectively, remain to be determined.…”

Evaluation of Immunologic Function of Peripheral Blood Monocytes from Schizophrenic Patients in Response to Toxoplasma Gondii

“…NO regulates the proliferation, functions, and fates of neural stem cells, and affects adult neurogenesis [47,48]. It also plays a pivotal role in neural differentiation, long-term potential (LTP) changes in the shape of synapses, memory, and learning [49][50][51][52]. Some studies have suggested that NO in the central nervous system (CNS) is cytoprotective at physiological concentrations and has a cytotoxic effect at higher levels [53][54][55].…”