Deletion of Melanin-Concentrating Hormone Receptor-1 gene accentuates D-amphetamine-induced psychomotor activation but neither the subsequent development of sensitization nor the expression of conditioned activity in mice
[en] The present study aimed to test the hypothesis that mice lacking the MCHR1 receptor (Melanin-Concentrating Hormone Receptor-1) present
an elevated vulnerability towards the neurobehavioural effects of D-amphetamine, presumably due to previously established up-regulations of
dopamine D1 receptors in these mice. We examined the psychomotor effects of five once-daily injections of 1.5 and 3 mg/kg D-amphetamine (i.p.)
or ten once-daily injections of 2.25 mg/kg D-amphetamine in knockout (KO) mice lacking the MCHR1 receptor. The first injection of Damphetamine
induced a greater psychomotor response amongst the KO mice at 2.25 and 3.0 mg/kg. On all subsequent D-amphetamine injections,
KO mice still showed greater levels of psychomotor activity than the WT mice, but with no between-genotype difference in the rate of
development of sensitization (similar slopes of the curves). Furthermore, 24 h after the last injection of 2.25 mg/kg D-amphetamine both genotypes
exhibited a significant post-sensitization conditioned activity. Thus, MCHR1 receptors are likely not deeply involved in the mechanisms of
induction of sensitization and related conditioned activity induced by D-amphetamine, albeit our results confirm a contribution of these receptors
to the mechanisms of the acute effects of that drug, possibly via an inhibitory action on the dopaminergic mesolimbic system. Our results do not
support the hypothesis of a functional contribution of MCHR1 receptors to the addictive effects of D-amphetamine
Research center :
Centre de Neurosciences Cognitives et Comportementales - ULiège
Disciplines :
Neurosciences & behavior
Author, co-author :
Tyhon, Amélie ✱; Université de Liège - ULiège > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér.
Lakaye, Bernard ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Grisar, Thierry ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Tirelli, Ezio ; Université de Liège - ULiège > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér.
✱ These authors have contributed equally to this work.
Language :
English
Title :
Deletion of Melanin-Concentrating Hormone Receptor-1 gene accentuates D-amphetamine-induced psychomotor activation but neither the subsequent development of sensitization nor the expression of conditioned activity in mice
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