Differential regulation of cocaine-induced locomotor activity in inbred long-sleep and short-sleep mice by dopamine and serotonin systems.
Acute injection of cocaine increases locomotor activity of inbred long-sleep (ILS) mice to a greater extent than inbred short-sleep (ISS) mice. Strain differences in dopamine and/or serotonin (5-HT) neurotransmission could underlie these behavioral differences. Here, we found that dopamine D1, 5-HT(2A) and 5-HT3 receptor antagonists reduced cocaine-stimulated activity selectively in ILS mice. In contrast, 5-HT transporter (SERT) or 5-HT(1A) receptor antagonists potentiated cocaine-stimulated activity in ISS, but not in ILS, mice; this potentiation in ISS mice was abolished by dopamine D1 receptor blockade. Thus, in ILS mice, cocaine-induced activation of D1, 5-HT(2A) or 5-HT3 receptors is sufficient to produce locomotor stimulation. In contrast, ISS mice require pharmacologically increased 5-HT levels, which appear to result in increased dopamine neurotransmission, for cocaine-induced activation. Our results demonstrate strain differences in dopamine/5-HT receptor subtypes and their interactions that contribute to the differential behavioral responsiveness of ILS and ISS mice to cocaine.
Department of Pharmacology and Neuroscience Program, University of Colorado Health, Sciences Center, Denver, CO, USA. taleen.hanania@psychogenetics.com
Taleen
T
Hanania
Andrew C
AC
McCreary
Danielle O
DO
Salaz
Anne M
AM
Lyons
Nancy R
NR
Zahniser
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics / Q000502:physiology*; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects* / Q000235:genetics*; D013045:Species Specificity
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005473:Fluoxetine; D003042:Cocaine