Environmental novelty modulates the induction and expression of single injection-induced behavioral sensitization to morphine.

Opioid addiction is a growing public health problem, being currently considered an epidemic in the United States. Investigating the behavioral effects of opioids and the factors influencing their development becomes of major importance. In animals, the effects of drugs of abuse can be assessed using the behavioral sensitization model, which shares similar neuronal substrates with drug craving in humans. Importantly, novelty plays a critical role on the development of behavioral sensitization. The aim of the present study was to investigate the influence of a new environment on both the induction and expression phases of morphine (Mor)-induced behavioral sensitization in the two-injection protocol. Mice were initially treated with saline, 15 or 30 mg/kg Mor (induction phase), and subsequently challenged 7 days later with 15 mg/Kg Mor (expression phase). Locomotor frequency was evaluated during behavioral sessions, performed as follow: induction session on a novel environment and expression on a familiar open-filed apparatus; induction session on animals' home-cage (familiar environment) and expression session on an unknown open-filed apparatus; both sessions on novel environments; and both sessions on familiar contexts. Mor-induced behavioral sensitization was only observed when animals were exclusively exposed to novelty during the induction phase, not being observed when both the induction and expression sessions were performed on similar (novel or familiar) environments. Our results suggest that the development of behavioral sensitization to Mor depends on the exposure to novelty during the induction phase and absence of novelty during the expression phase, indicating a complex relationship between novelty and Mor-induced behavioral effects.

Reciprocal interactions between MK-801, sleep deprivation and recovery in modulating rat behaviour.

Increasing evidence indicates that sleep deprivation alters behavioural responses to various pharmacological agents which might be associated to changes in receptor systems. The present work addressed the effects of sleep deprivation and recovery on behavioural changes induced by MK-801, and investigated whether such effects are related to changes in NMDA receptor (NMDAR) binding. Male Wistar rats were deprived of sleep for 96 h using the platform method (SD group), or were sleep deprived and then allowed to recover sleep for 24 h (SR group). Animals were treated with saline or 0.05, 0.10 or 0.20 mg/kg MK-801 before testing in an open field arena and elevated plus maze. A separate set of animals was sacrificed for [³H]MK-801 binding analysis in 40 brain regions. MK-801-induced hyperlocomotion was facilitated in a dose-dependent fashion after SR, while SD-induced increase in grooming was antagonized by the drug. Anxiolytic effects of 0.05 and 0.10 mg/kg MK-801 were unaffected by SD or SR conditions. No significant differences among groups were found in NMDAR binding. These findings indicate that the combined effects of MK-801 and sleep deprivation and recovery interact in a complex fashion to affect rat behaviour. They further suggest that such effects cannot be attributed to altered NMDAR binding in brain.