Opioid-environment interaction: Contrasting effects of morphine administered in a novel versus familiar environment on acute and repeated morphine induced behavioral effects and on acute morphine ERK activation in reward associated brain areas

• Published in: Behavioural brain research Vol. 476; p. 115221
• Main Authors: Coelho, Gabriela Corrêa, Crespo, Luiz Gustavo Soares Carvalho, Sampaio, Maria de Fátima dos Santos, Silva, Regina Claudia Barbosa, Samuels, Richard Ian, Carey, Robert J., Carrera, Marinete Pinheiro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.01.2025
• Subjects: Behavioral sensitization; Environmental novelty; ERK; Familiarity; Morphine; Morphine; Environmental novelty; Familiarity; Behavioral sensitization; ERK; familiarity; behavioral sensitization; environmental novelty
• ISSN: 0166-4328; 1872-7549; 1872-7549
• DOI: 10.1016/j.bbr.2024.115221

We report that environmental context can have a major impact on morphine locomotor behavior and ERK effects. We manipulated environmental context in terms of an environmental novelty/ familiarity dimension and measured morphine behavioral effects in both acute and chronic morphine treatment protocols. Wistar rats (n=7 per group) were injected with morphine 10 mg/kg or vehicle (s.c.), and immediately placed into an arena for 5 min, and locomotor activity was measured after one or 5 days. The morphine treatments were initiated either when the environment was novel or began after the rats had been familiarized with the arena by being given 5 daily nondrug tests in the arena. The results showed that acute and chronic morphine effects were strongly modified by whether the environment was novel or familiar. Acute morphine administered in a novel environment increased ERK activity more substantially in several brain areas, particularly in reward-associated areas such as the VTA in comparison to when morphine was given in a familiar environment. Repeated morphine treatments initiated in a novel environment induced a strong locomotor sensitization, whereas repeated morphine treatments initiated in a familiar environment did not induce a locomotor stimulant effect but rather a drug discriminative stimulus dis-habituation effect. The marked differential effects of environmental novelty/familiarity and ongoing dopamine activity on acute and chronic morphine treatments may be of potential clinical relevance for opioid drug addiction. •Environmental novelty is a modulator of acute and repeated effects of morphine.•In a novel environment, repeated MOR induced sensitization.•In a familiar environment, repeated MOR did not induce sensitization•In a novel environment acute MOR increased ERK activity.•MOR can reinforce prepotent behavior in a novel environment.