Abstract
Stress is known to modulate sensitisation to repeated psychostimulant exposure. However, there is no direct evidence linking glucocorticoids and sensitisation achieved by repeated administration of the NMDA receptor antagonist MK-801. We tested the hypothesis that co-administration of RU486, a glucocorticoid receptor (GR) antagonist, prior to repeated daily MK-801 injections would block the expression of locomotor sensitisation due to its dual effects on corticosterone and dopamine. We employed a repeated MK-801 administration locomotor sensitisation paradigm in male Sprague Dawley rats. RU486 or a dimethyl sulfoxide (DMSO) vehicle was co-administered with MK-801 or saline during the induction phase. Subsequent to withdrawal, rats were challenged with MK-801 alone to test for the expression of sensitisation. In a separate cohort of rats, plasma corticosterone levels were quantified from blood samples taken on the 1st, 4th and 7th day of induction and at expression. One day after challenge, nucleus accumbens tissue levels of dopamine and its metabolites DOPAC and HVA were measured. During the induction phase, RU486 progressively enhanced locomotor sensitisation to MK-801. RU486 and MK-801 both showed stimulatory effects on corticosterone levels and this was further augmented when given in combination. Contrary to our hypothesis, RU486 did not block the expression of locomotor sensitisation to MK-801 and actually increased levels of dopamine, DOPAC and HVA in nucleus accumbens tissue. Our results showed that RU486 has augmentative rather than inhibitory effects on MK-801-induced sensitisation. This study indicates a divergent role for glucocorticoids in sensitisation to MK-801 compared to sensitisation with other psychostimulants.
Highlights
Sensitisation can be defined as the enhanced behavioural or neurochemical response to a drug following repeated psychostimulant exposure
In the RU486 pre-treated rats, repeated measures ANOVA revealed a significant Day x Drug treatment interaction (F1,14 = 59.5, p
This study investigated the role of glucocorticoid receptor (GR) signalling in a model of MK-801 sensitisation in male Sprague Dawley rats
Summary
Sensitisation can be defined as the enhanced behavioural or neurochemical response to a drug following repeated psychostimulant exposure. Behavioural sensitisation is typically observed as an augmented hyperlocomotor response to a drug challenge after withdrawal from repeated drug administration. This phenomenon is typically studied to understand. The induction of sensitisation refers to the neurological changes that develop with repeated drug exposure, whereas the expression of sensitisation is characterized as the enhanced response to a drug challenge [3]. The ability of different classes of drugs of abuse to induce sensitisation is indicative of the multiple mechanisms involved in these behavioural and neurochemical adaptations [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
