Biomedical subjects

Mohammad-Reza Zarrindast

Publications and source records attributed to Mohammad-Reza Zarrindast.

At least 19 recordsLinked to original sources

PubMed2006

Effects of clozapine and sulpiride on morphine state-dependent memory in the step-down passive avoidance test.

The effects of antipsychotic drugs sulpiride and clozapine on morphine state-dependent memory of passive avoidance task were examined in mice. Post-training administration of morphine (5 mg/kg) led to state-dependent learning with impaired memory retrieval on the test day which was reversed by pre-test administration of the same dose of the opioid (5 mg/kg). In animals where memory was impaired by post-training morphine, the administration of either sulpiride or clozapine before pre-test morphine reduced the improvement of memory produced by the opioid. Co-administration of sulpiride with clozapine did not potentiate their antagonistic response. In conclusion, the inhibition of improvement of memory retrieval by morphine treatment on the test day by the two dopamine receptor antagonists seems to be induced through two different receptor mechanisms.

Analgesics, Opioid↗

PubMed2006

Morphine-induced place preference: involvement of the central amygdala NMDA receptors.

In the present study, the effects of bilateral injections of N-methyl-d-aspartate (NMDA) receptor agonist and/or antagonist into the central amygdala (CeA) on the acquisition and expression of morphine-induced conditioned place preference (CPP) were investigated in male Wistar rats. Animals that received 3 daily subcutaneous (s.c.) injections of morphine (1-9 mg/kg) or saline (1.0 ml/kg) indicated a significant preference for compartment paired with morphine in a dose dependent manner. Intra-CeA administration of the NMDA (0.01, 0.1 or 1 microg/rat) with an ineffective dose of morphine (1 mg/kg, s.c.) elicited a significant CPP. Administration of the non-competitive NMDA receptor antagonist, MK-801 (0.1, 0.3 or 0.5 microg/rat), into the central amygdala dose-dependently inhibited the morphine (6 mg/kg, s.c.)-induced place preference. Furthermore, intra-CeA administration of MK-801 (0.25, 0.5 or 1 microg/rat) reduced the response induced by NMDA (1 microg/rat, intra-CeA) plus morphine (1 mg/kg, s.c.). Neither NMDA nor MK-801 alone produce a significant place preference or place aversion. Moreover, intra-CeA injection of NMDA but not MK-801 before testing significantly increased the expression of morphine (6 mg/kg, s.c.)-induced place preference. NMDA or MK-801 injections into the CeA had no effects on locomotor activity on the testing sessions. These results suggest that the NMDA receptor mechanisms in the central amygdala may be involved in the acquisition and expression of morphine-induced place preference.

Amygdala↗

PubMed2006

Intra-hippocampal inhibition of protein kinase AII attenuates morphine-induced conditioned place preference.

Morphine and other drugs of abuse modulate protein kinase A (PKA) signaling within the mesolimbic reward pathway. Using a balanced conditioned place preference (CPP) paradigm, we studied the possible involvement of protein kinase AII (PKA II) on the acquisition, expression and consolidation of morphine place conditioning in male Wistar rats. Subcutaneous administration of various doses of morphine sulfate (1-9 mg/kg) induced CPP in a dose-dependent manner. H-89, a selective PKA II inhibitor, was administered into CA1 region of the hippocampus at 1, 2.5 and 5 microM/rat. Using a 3-day schedule of conditioning, it was found that the H-89 did not produce a significant place preference or place aversion. H-89 (1, 2.5 and 5 microM/rat) significantly reduced the time spent by rats in the morphine compartment when given immediately after each conditioning session (consolidation), whereas it had no effect when administered before morphine during the conditioning phase (acquisition) or before testing for place preference in the absence of morphine (expression). It is concluded that the PKA II may play an active role in the consolidation of reward-related memory of morphine in CA1 region of the hippocampus.

Animals↗

PubMed2006

The effects of histaminergic agents in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety.

High levels of histamine are found in the hippocampus. The central histamine system is involved in many physiological behavioural processes including anxiety-related behaviours both in animals and humans. In the present study, we investigated the effects of intra-hippocampal CA1 (intra-CA1) microinjection of histaminergic agents on anxiety-related behaviours in rats, using elevated plus-maze test of anxiety. Intra-CA1 administration of histamine (at the dose of 10 microg/rat) increased open arm time (%OAT) and open arm entry (%OAE) but not locomotor activity, thus showing an anxiolytic response. Intra-CA1 microinjection of pyrilamine (H1 receptor antagonist; at the doses of 10, 20 and 40 microg/rat) in combination with histamine (10 microg/rat) showed a decrease in the %OAT and %OAE. Higher dose of the antagonist (40 microg/rat) by itself increased both %OAT and %OAE, but not locomotor activity, indicating an anxiolytic effect. Intra-CA1 microinjection of ranitidine (H2 receptor antagonist), at the doses of 10, 20 and 40 microg/rat, also reduced the histamine response. Furthermore, the H2 receptor antagonist by itself reduced %OAT and %OAE without affecting locomotor activity. The results may indicate an anxiogenic effect for the antagonist. Our results showed that histamine may modulate anxiety via H1 and H2 receptors in the CA1 region of hippocampus of the rat.

Animals↗

PubMed2006

The role of nitric oxide within the nucleus accumbens on the acquisition and expression of morphine-induced place preference in morphine sensitized rats.

In the present study, the effects of intra-accumbal administration of L-arginine, a nitric oxide precursor, and N(G)-nitro-L-arginine methyl-ester (L-NAME), a nitric oxide synthase inhibitor, on the acquisition and expression of morphine-induced place conditioning in morphine-sensitized rats were studied. Subcutaneous (s.c.) administration of morphine (2.5, 5 and 7.5 mg/kg) induced conditioned place preference. Repeated pretreatment of morphine (5 mg/kg, i.p.) followed by 5 days without drug treatment, increased conditioning response induced by morphine (0.25, 0.5 and 0.75 mg/kg). Intra-accumbal (intra-nucleus accumbens; 1 microg/rat) administration of L-arginine (0.3, 1 and 3 microg/rat) significantly increased or reduced the acquisition of morphine place conditioning in non-sensitized and sensitized rats respectively. However, the drug reduced expression of place conditioning by morphine in sensitized animals. Intra-nucleus accumbens injections of L-NAME (0.3, 1 and 3 microg/rat) reduced the acquisition and expression of morphine place conditioning in the sensitized animals. The results indicate that nitric oxide (NO) within the nucleus accumbens is involved in the acquisition and expression of morphine place conditioning in morphine-sensitized rats.

Animals↗

PubMed2006

Influence of morphine and dopamine receptor sensitization on locomotor activity in mice.

In the present study, the influence of morphine- and dopamine receptor antagonists-induced sensitization on morphine-induced locomotion in mice was investigated. Morphine (30, 40 and 50 mg/kg) increased, while lower doses of the opioid (10 and 20 mg/kg) decreased locomotor activity of mice. Subchronic repeated pretreatment of animals with morphine showed an increase in locomotion induced by the opioid. Clozapine reduced locomotor activity induced by morphine in both the naïve and subchronic morphine-treated animals. Subchronic pretreatment of clozapine also caused an increase in the locomotion induced by morphine. Sulpiride also decreased locomotion induced by morphine and its subchronic administration of the drug caused an increase in morphine- or apomorphine-induced locomotion. Co-administration of clozapine with sulpiride did not elicit potentiation in inhibiting the morphine effect. The D2 receptor mRNA expression was also increased by repeated morphine administration. It may be concluded that morphine-induced sensitization may be due to increase in D2 receptor mRNA expression. Sulpiride and clozapine may induce sensitization and also inhibit morphine-induced locomotion through their dopamine receptor blocking properties.

Animals↗

PubMed2006

Dorsal hippocampal dopamine receptors are involved in mediating ethanol state-dependent memory.

In the present study, the effects of bilateral injections of dopaminergic agents into the hippocampal CA1 regions (intra-CA1) on ethanol (EtOH) state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intra-peritoneal (i.p.) administration of EtOH (0.25, 0.5 and 1 g/kg) dose dependently induced impairment of memory retention. Pre-test administration of EtOH (0.5 g/kg)-induced state-dependent retrieval of the memory acquired under pre-training EtOH (0.5 g/kg) influence. Intra-CA1 administration of the dopamine D(1) receptor agonist, SKF 38393 (0.5, 1 and 2 g/mouse) or the dopamine D(2) receptor agonist, quinpirole (0.25, 0.5 and 1 microg/mouse) alone cannot affect memory retention. While, pre-test intra-CA1 injection of SKF 38393 (2 microg/mouse, intra-CA1) or quinpirole (0.25, 0.5 and 1 microg/mouse, intra-CA1) improved pre-training EtOH (0.5 g/kg)-induced retrieval impairment. Moreover, pre-test administration of SKF 38393 (0.5, 1 and 2 microg/mouse, intra-CA1) or quinpirole (0.5 and 1 microg/mouse, intra-CA1) with an ineffective dose of EtOH (0.25 g/kg) significantly restored the retrieval and induced EtOH state-dependent memory. Furthermore, pre-training injection of the dopamine D(1) receptor antagonist, SCH 23390 (4 microg/mouse), but not the dopamine D(2) receptor antagonist, sulpiride, into the CA1 regions suppressed the learning of a single-trial passive avoidance task. Pre-test intra-CA1 injection of SCH 23390 (2 and 4 microg/mouse, intra-CA1) or sulpiride (2.5 and 5 microg/mouse, intra-CA1) 5 min before the administration of EtOH (0.5 g/kg, i.p.) dose dependently inhibited EtOH state-dependent memory. These findings implicate the involvement of a dorsal hippocampal dopaminergic mechanism in EtOH state-dependent memory and also it can be concluded that there may be a cross-state dependency between EtOH and dopamine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2006

Influence of ATP-dependent K+ channels on nicotine-induced inhibition of withdrawal in morphine-dependent mice.

In the present study, we have investigated the effect of nicotine and diazoxide, a potassium channel opener and glibenclamide, a potassium channel (K(ATP)) blocker on naloxone-precipitated physical withdrawal signs, including jumping and diarrhea. Then, the interactions of nicotine with diazoxide and glibenclamide were tested. Mice were rendered dependent on morphine by subcutaneous (s.c.) injections of morphine sulphate 3 times a day for 3 days, and jumping behavior and diarrhea were induced by intraperitoneal (i.p.) administration of naloxone 2 h after the 10th injection of morphine sulphate on day 4. Nicotine was administered 15 min and diazoxide and glibenclamide 30 min before naloxone injection. Nicotine (0.01-1 mg/kg, s.c.) and (0.1-1 mg/kg) reduced withdrawal jumping and diarrhea respectively. Diazoxide (8-64 mg/kg, i.p.) decreased jumping behavior significantly, but had no significant effect on diarrhea. On the other hand glibenclamide (0.25-1 mg/kg i.p.) and (1 mg/kg) augmented jumping and diarrhea respectively. The response of nicotine on jumping or on diarrhea was potentiated by diazoxide and decreased by glibenclamide pretreatment. The isobolographic analysis revealed synergistic interaction between diazoxide and nicotine on decreasing physical withdrawal signs including jumping and diarrhea in morphine-dependent mice. According to these results the interaction of nicotine with the K(ATP) channel opener and blocker in morphine physical withdrawal signs could be explained by direct and indirect effects of nicotine on membrane potassium currents.

Adenosine Triphosphate↗

PubMed2006

Influence of ATP-sensitive potassium channels on lithium state-dependent memory of passive avoidance in mice.

The effects of ATP-sensitive potassium channels on lithium induced state-dependent memory of passive avoidance task were examined in mice. The pre-training (5 mg/kg) and pre-test (5 mg/kg) injection of lithium impaired memory retrieval on the test day. Impairment of pre-training lithium was restored by pre-test administration of lithium (5 mg/kg), diazoxide, an ATP-sensitive potassium channel opener, (15, 30 and 60 mg/kg) or glibenclamide, an ATP-sensitive potassium channel blocker, (6 and 18 mg/kg). Pre-test administration of inactive doses of lithium (2.5 and 10 mg/kg) plus lower and inactive dose of glibenclamide (2 mg/kg) or diazoxide (1.5 mg/kg) also reversed the amnesia induced by pre-training lithium (5 mg/kg). In conclusion, the ATP-sensitive potassium channel opener or blocker not only mimicked the effect of lithium in state-dependent learning in the absence of lithium on the test day, but also potentiated the effect of low dose of lithium in restoration of memory. Therefore, ATP-sensitive potassium channels may have a modulatory influence on lithium response.

Animals↗

PubMed2006

Influence of acute and sub-chronic nicotine pretreatment on morphine state-dependent learning.

In the present study, the effects of acute and sub-chronic pretreatment of nicotine on impairment of memory formation and the state-dependent learning by morphine have been investigated in mice. Pre-training administration of morphine (5mg/kg) decreased the learning of a one-trial passive avoidance task, which was reversed by pre-test administration of the same dose of morphine. Amnesia induced by pre-training morphine was also significantly reversed in nicotine (0.001, 0.01 and 0.1 mg/kg)-treated animals on the test day. Morphine induced amnesia was also reversed in animals which had previously received sub-chronic injections of nicotine, once daily for 3 days followed by 14 days of no drug treatment. The restoration of memory by pre-test morphine was also reduced in animals which had previously received once daily injections of atropine (0.25, 0.5 and 1 mg/kg, i.p.) for 3 days after 14 of being days drug free. In the animals, restoration of memory by sub-chronic nicotine administration, was also decreased by once daily administration of atropine (0.25, 0.5 and 1 mg/kg) 10 min prior to injection of nicotine (0.1 microg/kg/day, for 3 days) but not with SCH 23390; R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl (0.01, 0.05 and 0.1 mg/kg) or sulpiride (25, 50 and 100 mg/kg) during 3-days of treatment with nicotine. The results suggest that nicotine may induce sensitization which affects the impairment of memory formation via cholinergic but not dopaminergic systems.

Analysis of Variance↗

PubMed2006

Morphine state-dependent learning sensitization and interaction with nitric oxide.

In the present study, the effects of nitric oxide (NO) precursor L-arginine and L-NAME, a potent inhibitor of NO synthase (NOS), on the expression of sensitization of morphine were investigated. Pre-training administration of morphine (5 mg/kg) impaired memory retrieval compared to pre-training saline-treated animals. Amnesia due to pre-training morphine (5 mg/kg) was restored by pre-test morphine (5 mg/kg). The retrieval impairment was also inhibited in mice which had received once-daily injections of morphine (20 and 30 mg/kg, s.c.) for 3 days, followed by 5 days of no drug treatment before training (in order to induce morphine sensitization). Administration of L-arginine (60 mg/kg/day - 3 days) or L-NAME (20 mg/kg/day - 3 days) before training did not alter morphine state dependency. During acquisition of sensitization, administration of L-arginine (60 mg/kg) 20 min before morphine (10 mg/kg/day, for 3 days) increased, while injection of L-NAME (20 mg/kg) 20 min before morphine (30 mg/kg/day, for 3 days) decreased morphine state dependency. It is concluded that NO is involved in the morphine-induced sensitization.

Animals↗

PubMed2006

Histaminergic receptors of medial septum and conditioned place preference: D1 dopamine receptor mechanism.

In the present study, the effects of intra-medial septum injections of histamine and/or the histamine H1 or H2 receptor antagonists on the acquisition of conditioned place preference (CPP) in male Wistar rats have been investigated. Our data showed that the conditioning treatments with intra-medial septum injection of different doses of histamine (0.5-15 microg/rat) induced a significant CPP for the drug-associated place. Using a 3-day schedule of conditioning, it was found that the histamine H1 receptor antagonist, pyrilamine (10 and 15 microg/rat, intra-medial septum) also induced a significant place preference. In addition, pyrilamine inhibited the histamine (7.5 microg/rat)-induced place preference. Intra-medial septum administration of the histamine H2 receptor antagonist, ranitidine (5-15 microg/rat) alone or in combination with histamine did not produce a significant place preference or place aversion. On the other hand, intra-medial septum administration of the dopamine D1 receptor antagonist, SCH 233390 (0.5, 0.75 and 1 microg/rat) inhibited the histamine (7.5 microg/rat) or pyrilamine (15 microg/rat)-induced place preference in a dose-dependent manner, but no effect was observed for the dopamine D2 receptor antagonist, sulpiride on the histamine or pyrilamine response. The administration of histamine (2.5-15 microg/rat) or pyrilamine (10 and 15 microg/rat) during acquisition increased locomotor activity of the animals on the testing days. The results suggest that histaminergic receptors of the medial septum may be involved in CPP and thus it is postulated that dopamine D1 receptors may play an important role in this effect.

Analysis of Variance↗

PubMed2006

Influence of intracerebroventricular administration of dopaminergic drugs on morphine state-dependent memory in the step-down passive avoidance test.

The effects of dopaminergic drugs on morphine state-dependent memory of passive avoidance task were examined in mice. Pre-training administration of morphine (5mg/kg) led to state-dependent learning with impaired memory retrieval on the test day which was reversed by pre-test administration of the same dose of the opiate. The pre-test intracerebroventricular (i.c.v.) administration of the dopamine D1 receptor agonist (SKF38393), dopamine D2 receptor agonist (quinpirole) and dopamine D2 receptor antagonist (sulpiride) not only reversed the effect of pre-training morphine treatment, but also increased this action of the drug. Furthermore, the pre-test i.c.v. administration of dopamine D1 receptor antagonist (SCH23390) prevented the restoration of memory by morphine. In conclusion, the morphine-induced recovery of memory, on the test day, seems to be induced, at least in part, through dopamine receptors.

Analysis of Variance↗

PubMed2006

Influence of morphine- or apomorphine-induced sensitization on histamine state-dependent learning in the step-down passive avoidance test.

Effects of morphine- or apomorphine-induced sensitization on histamine state-dependent memory of passive avoidance task were examined in mice. Pre-training intracerebroventricular (i.c.v.) administration of histamine (20 microg/mouse) decreased the learning of a one-trial passive avoidance task. Pre-test administration of histamine (10 and 20 microg/mouse) reversed amnesia induced by pre-training of histamine, with maximum response at 20 microg/mouse. Pre-training histamine-induced amnesia was also reversed in morphine- or apomorphine-sensitized mice that had previously received once daily injections of morphine (20 and 30 mg/kg) or apomorphine (0.5 and 1 mg/kg) for 3 days. The reversion of histamine-induced amnesia in morphine-sensitized mice was decreased by once daily administration of naloxone (0.5 and 1 mg/kg), SCH 23390 (0.05 and 0.1 mg/kg) or sulpiride (25, 50 and 100 mg/kg) prior to injection of morphine (30 mg/kg/day, 3 days). Furthermore, once daily administration of sulpiride (50 and 100 mg/kg) but not SCH 23390 (0.01, 0.05 and 0.1 mg/kg) prior to apomorphine (1 mg/kg, for 3 days) decreased the reversion of pre-training histamine-induced amnesia by apomorphine. The results suggest that apomorphine or morphine sensitization affects the impairment of memory induced by histamine and thus it is postulated that opioid and dopamine receptors may play an important role in this effect.

Animals↗

PubMed2006

Influence of nitric oxide on morphine-induced amnesia and interactions with dopaminergic receptor agents.

The interactions of dopaminergic receptors and nitric oxide (NO) with morphine-induced memory of passive avoidance have been investigated in mice. Pre-training administration of morphine (1, 3 and 5 mg/kg, s.c.) dose-dependently decreased the learning of a one-trial passive avoidance task. Pre-training administration of L-arginine, a nitric oxide precursor (50, 100 and 200 mg/kg, i.p.), alone did not affect memory formation. The drug (100 and 200 mg/kg) decreased significantly amnesia induced by pre-training morphine (5 mg/kg). Pre-training administration of L-NAME (N(G)-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor (20 and 30 mg/kg, i.p.), dose-dependently impaired memory formation. In addition, co-pretreatment of different doses of L-NAME (10, 20 and 30 mg/kg) with lower dose of morphine (1 mg/kg), which did not induce amnesia by itself, caused inhibition of memory formation. Pre-training administration of apomorphine, a dopaminergic receptor agonist (0.25, 0.5 and 1 mg/kg, i.p.), alone also did not affect memory formation, but morphine-induced amnesia was significantly inhibited by pretreatment with apomorphine (0.5 and 1 mg/kg, 5 min, i.p.). On the other hand, the inhibition of morphine-induced amnesia by L-arginine (200 mg/kg, i.p.) was significantly decreased by pretreatment with different doses of dopamine D1 receptor antagonist, SCH 23390 (0.001, 0.01 and 0.1 mg/kg, i.p.) or D2 receptor antagonist, sulpiride (12.5, 25, 50 and 100 mg/kg, i.p.). However, the dopamine receptor antagonists could not affect memory formation by themselves. It may be concluded that the morphine-induced impairment of memory formation can be prevented by nitric oxide donor and, in this effect, dopaminergic mechanism is involved.

Amnesia↗

PubMed2006

GABA(A) receptors of hippocampal CA1 regions are involved in the acquisition and expression of morphine-induced place preference.

In the present study, the effects of bilateral intra-hippocampal CA1 (intra-CA1) injections of GABA(A) receptor agonist and/or antagonist on the acquisition and expression of morphine-induced place preference in male Wistar rats have been investigated. The conditioning treatments with subcutaneous (s.c.) injections of different doses of morphine (0.5-7.5 mg/kg) induced a conditioned place preference (CPP) for the drug-associated place in a dose-dependent manner. Intra-CA1 administration of the GABA(A) receptor agonist, muscimol (0.25, 0.5 and 1 microg/rat) significantly inhibited the morphine (5 mg/kg, s.c.)-induced CPP. Intra-CA1 injections of different doses of the GABA(A) receptor antagonist, bicuculline (0.25, 0.5 and 1 microg/rat), in combination with an ineffective dose of morphine (0.5 mg/kg, s.c.) elicited a significant CPP. However, muscimol or bicuculline by themselves did not elicit any effect on place conditioning. Furthermore, the muscimol-induced inhibition of morphine response was reversed by bicuculline (1 microg/rat, intra-CA1) administration. On the other hand, the bilateral intra-CA1 injections of muscimol (0.25, 0.5 and 1 microg/rat) or bicuculline (0.5, 1 and 2 microg/rat) significantly decreased the expression of morphine-induced CPP. Intra-CA1 administration of different doses of muscimol or bicuculline had no effect on locomotor activity in the testing phase. Our data indicated that the GABA(A) receptors of the hippocampal CA1 regions may play an important role in the acquisition and expression of morphine-induced place preference.

Analysis of Variance↗

PubMed2006

The effects of histaminergic agents in the ventral hippocampus of rats in the plus-maze test of anxiety-like behaviours.

It has been suggested that histamine have modulatory influence on anxiety-related behaviours both in animals and humans. Ventral hippocampus (VHC) may also be an important brain site in the modulation of fear or anxiety. In the present study, the effects of histaminergic agents on anxiety-related behaviours in the rats, using plus-maze test has been investigated. Intra-VHC administration of histamine (2.5, 5 and 7.5 microg/rat) decreased %OAT and %OAE but not locomotor activity, showing an anxiogenic response. Pretreatment of animals with either pyrilamine, a H1 receptor antagonist (10 microg/rat), or ranitidine, a H2 receptor antagonist (10 microg/rat) reverse anxiogenic response of histamine (2.5, 5 and 7.5 microg/rat). However, intra-VHC microinjection of higher doses of pyrilamine (40 microg/rat) or ranitidine (20 and 40 microg/rat) alone increased anxiety-like behaviours in rats. Our results showed that histamine may modulate anxiety-like behaviours via H1 and H2 receptors in the ventral hippocampus of the rats.

Analysis of Variance↗

PubMed2006

Repeated administration of dopaminergic agents in the nucleus accumbens and morphine-induced place preference.

In the present study, the effects of repeated intra nucleus accumbens (intra-NAc) injections of dopamine receptor agents on morphine-induced conditioned place preference (CPP) in rats were investigated by using an unbiased 3-days schedule of place conditioning design. The animals receiving once daily subcutaneous (s.c.) injections of morphine (0.5-7.5mg/kg) or saline (1.0 ml/kg, s.c.) showed a significant place preference in a dose-dependent manner. The maximum response was observed with 5mg/kg of the opioid. Three days intra-NAc injections of apomorphine (0.5 and 1 microg/rat) followed by 5 days free of the drug, increased or decreased, respectively CPP induced by the lower dose of morphine (0.5mg/kg, s.c.). Morphine-induced CPP was also significantly increased in the animals that had previously received the 3-days intra-NAc injections of SKF 38393 (4 and 8 microg/rat) or quinpirole (2 and 4 microg/rat, intra-NAc). The CPP induced by a higher dose of morphine (5mg/kg, s.c.) was significantly decreased in the animals that had previously received the 3-days SCH 23390 (0.005 and 0.01 microg/rat; intra-NAc). On the other hand, the CPP induced by morphine (5mg/kg, s.c.) was significantly increased in the animals that had previously received the 3-days sulpiride administration (5 microg/rat, intra-NAc). The 3-days administration of apomorphine, SKF 38393 or quinpirole, but not SCH 23390 and sulpiride reduced the locomotor activity in the test session. It is concluded that repeated injections of dopamine receptors agents followed by 5 days free of the drugs in the NAc can affect morphine reward.

Animals↗