TY - JOUR
T1 - Methadone does not alter key parameters of adult hippocampal neurogenesis in the heroin-naïve rat
AU - Sankararaman, Aparna
AU - Masiulis, Irene
AU - Richardson, Devon R.
AU - Andersen, Jannike M.
AU - Mørland, Jørg
AU - Eisch, Amelia J.
N1 - Funding Information:
These studies were generously supported by the Norwegian Institute of Public Health (Nasjonalt Folkehelseinstitutt)/University of Oslo, Norway . The authors thank Dr. Bryon Adinoff for helpful conversations during the writing of the manuscript.
PY - 2012/5/10
Y1 - 2012/5/10
N2 - Methadone is a synthetic opiate that is useful in a variety of clinical settings, including in maintenance therapy of heroin dependence and as an analgesic. However, methadone can have negative effects on cognition in humans and in rodents. The mechanisms underlying methadone-induced disruption in cognition are unknown. One possibility is that methadone disrupts adult hippocampal neurogenesis, a form of hippocampal plasticity involved in cognition that is disrupted by other opiates, like morphine. The goal of this study was to determine if methadone alters key parameters of hippocampal neurogenesis in the adult rat. Four groups of male rats were injected with saline (Saline, . n=. 11) or methadone (Escalating, Short Term, Acute, . n=. 10-11/group) over the course of three weeks. Weight gain, locomotor activity, and neurogenesis data were collected. Consistent with prior results, Escalating rats had slower weight gain (-4% vs. Saline). Also consistent with prior results, methadone did not alter locomotor activity over the course of a 90. min test. However, closer analysis revealed that methadone - irrespective of the dose or duration - led to a decrease in locomotor activity (-11 to -20% vs. saline) when examined during the first 5. min of the locomotor test. Surprisingly, methadone did not alter any of three quantified parameters relevant to adult hippocampal neurogenesis (number of Ki67-, doublecortin-, or BrdU-immunoreactive cells [BrdU given prior to saline/methadone exposure]). These results suggest that - unlike other opiates such as morphine - experimenter-delivered methadone does not alter hippocampal plasticity by decreasing the number of adult-generated neurons.
AB - Methadone is a synthetic opiate that is useful in a variety of clinical settings, including in maintenance therapy of heroin dependence and as an analgesic. However, methadone can have negative effects on cognition in humans and in rodents. The mechanisms underlying methadone-induced disruption in cognition are unknown. One possibility is that methadone disrupts adult hippocampal neurogenesis, a form of hippocampal plasticity involved in cognition that is disrupted by other opiates, like morphine. The goal of this study was to determine if methadone alters key parameters of hippocampal neurogenesis in the adult rat. Four groups of male rats were injected with saline (Saline, . n=. 11) or methadone (Escalating, Short Term, Acute, . n=. 10-11/group) over the course of three weeks. Weight gain, locomotor activity, and neurogenesis data were collected. Consistent with prior results, Escalating rats had slower weight gain (-4% vs. Saline). Also consistent with prior results, methadone did not alter locomotor activity over the course of a 90. min test. However, closer analysis revealed that methadone - irrespective of the dose or duration - led to a decrease in locomotor activity (-11 to -20% vs. saline) when examined during the first 5. min of the locomotor test. Surprisingly, methadone did not alter any of three quantified parameters relevant to adult hippocampal neurogenesis (number of Ki67-, doublecortin-, or BrdU-immunoreactive cells [BrdU given prior to saline/methadone exposure]). These results suggest that - unlike other opiates such as morphine - experimenter-delivered methadone does not alter hippocampal plasticity by decreasing the number of adult-generated neurons.
KW - BrdU
KW - Dentate gyrus
KW - Doublecortin
KW - Ki67
KW - Locomotor activity
KW - Subgranular zone
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U2 - 10.1016/j.neulet.2012.03.066
DO - 10.1016/j.neulet.2012.03.066
M3 - Article
C2 - 22487733
AN - SCOPUS:84860249363
SN - 0304-3940
VL - 516
SP - 99
EP - 104
JO - Neuroscience letters
JF - Neuroscience letters
IS - 1
ER -