Ba. Mattingly et al., Repeated treatments with 7-OH-DPAT: Context-independent behavioral sensitization and conditioned hyperactivity, PHARM BIO B, 65(2), 2000, pp. 241-246
The primary objective of this study was to determine whether the expression
of behavioral sensitization to the putative dopamine D-3 receptor agonist
7-OH-DPAT is context dependent. Three groups (n = 8 each) of male Wistar ra
ts (250-350 g) were given nine injections (at 48-h intervals) of 7-OH-DPAT
(1.0 mg/kg, SC) or vehicle 15 min before and after activity testing. The pa
ired group received 7-OH-DPAT before activity testing and vehicle after tes
ting. The unpaired group received vehicle before and 7-OH-DPAT after testin
g, and the vehicle control group received two vehicle injections. Locomotor
activity was measured in photocell arenas for 2 h. After the first seven s
essions, all rats were tested for activity following a vehicle injection to
test for possible conditioning effects. Prior to the 11th session, all rat
s were given a challenge injection of 7-OH-DPAT (1.0 mg/kg, SC) to test for
sensitization. Major findings were as follows: (a) the 7-OH-DPAT/paired gr
oup displayed a progressively greater increase in locomotor activity with r
epeated treatments; (b) the 7-OH-DPAT/paired group was significantly more a
ctive than either the vehicle control group or the 7-OH-DPAT/unpaired group
during the vehicle test session; and (c) after the 7-OH-DPAT challenge inj
ection, the paired and unpaired 7-OH-DPAT groups were significantly, and eq
ually, more active than the vehicle control group. In contrast to previous
findings with the D-2-type dopamine agonists bromocriptine and quinpirole,
these results suggest that the expression of behavioral sensitization to 7-
OH-DPAT is not context dependent. Moreover, these results suggest that the
apparent conditioned hyperactivity and context dependency often observed af
ter repeated dopamine agonist treatments may not be related to the same ass
ociative and/or nonassociative mechanisms. (C) 2000 Elsevier Science Inc.