TY - JOUR
T1 - Repeated and chronic morphine administration causes differential long-lasting changes in dopaminergic neurotransmission in rat striatum without changing its δ- and κ-opioid receptor regulation
AU - Tjon, Guno H.K.
AU - De Vries, Taco J.
AU - Ronken, Eric
AU - Hogenboom, François
AU - Wardeh, George
AU - Mulder, Arie H.
AU - Schoffelmeer, Anton N.M.
PY - 1994/2/3
Y1 - 1994/2/3
N2 - Repeated, once daily morphine treatment (14 days) as well as chronic morphine administration (6 days) caused a rebound reduction in the electrically evoked release of [3H]dopamine from superfused rat striatal slices 1 day after the last subcutaneous injection. Interestingly, whereas [3H]dopamine release remained significantly reduced for at least 3 weeks following morphine withdrawal in chronically treated (tolerant/dependent) rats, neurotransmitter release from dopaminergic nerve terminals gradually increased above control values following cessation of repeated morphine administration. Postsynaptically, dopamine D1 receptor-stimulated adenylate cyclase appeared to be sensitized 1-3 days but was unchanged 3 weeks after chronic morphine treatment. In contrast, such an enhanced postsynaptic dopamine D1 receptor efficacy did not occur 1-3 days following repeated morphine administration, but appeared to develop slowly resulting in a profound increase of dopamine-sensitive adenylate cyclase 3 weeks after the last injection. The inhibitory effect of dynorphin A-(1-13) on [3H]dopamine release, as well as that of [Met5]enkephalin on dopamine D1 receptor-stimulated adenylate cyclase appeared to be unchanged subsequent to repeated or chronic morphine treatment. These data indicate that, long after cessation of drug treatment, chronic morphine treatment causes a reduction whereas repeated morphine administration gradually induces an enhancement of opioid receptor-regulated dopaminergic neurotransmission due to local adaptive changes within the rat striatum. Such distinct long-lasting alterations of dopaminergic neurotransmission induced by different temporal patterns of morphine administration in projection areas of mesencephalic dopaminergic neurons may be related to the enduring effects of drug abuse such as behavioural sensitization and drug craving.
AB - Repeated, once daily morphine treatment (14 days) as well as chronic morphine administration (6 days) caused a rebound reduction in the electrically evoked release of [3H]dopamine from superfused rat striatal slices 1 day after the last subcutaneous injection. Interestingly, whereas [3H]dopamine release remained significantly reduced for at least 3 weeks following morphine withdrawal in chronically treated (tolerant/dependent) rats, neurotransmitter release from dopaminergic nerve terminals gradually increased above control values following cessation of repeated morphine administration. Postsynaptically, dopamine D1 receptor-stimulated adenylate cyclase appeared to be sensitized 1-3 days but was unchanged 3 weeks after chronic morphine treatment. In contrast, such an enhanced postsynaptic dopamine D1 receptor efficacy did not occur 1-3 days following repeated morphine administration, but appeared to develop slowly resulting in a profound increase of dopamine-sensitive adenylate cyclase 3 weeks after the last injection. The inhibitory effect of dynorphin A-(1-13) on [3H]dopamine release, as well as that of [Met5]enkephalin on dopamine D1 receptor-stimulated adenylate cyclase appeared to be unchanged subsequent to repeated or chronic morphine treatment. These data indicate that, long after cessation of drug treatment, chronic morphine treatment causes a reduction whereas repeated morphine administration gradually induces an enhancement of opioid receptor-regulated dopaminergic neurotransmission due to local adaptive changes within the rat striatum. Such distinct long-lasting alterations of dopaminergic neurotransmission induced by different temporal patterns of morphine administration in projection areas of mesencephalic dopaminergic neurons may be related to the enduring effects of drug abuse such as behavioural sensitization and drug craving.
KW - Adenylate cyclase
KW - Dopamine release
KW - Morphine
KW - Opioid receptor
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=0028105821&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/0014-2999(94)90598-3
DO - https://doi.org/10.1016/0014-2999(94)90598-3
M3 - Article
C2 - 7908881
SN - 0014-2999
VL - 252
SP - 205
EP - 212
JO - European journal of pharmacology
JF - European journal of pharmacology
IS - 2
ER -