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6th Internet World Congress for Biomedical Sciences

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Differential effects of 18-Methoxycoronaridine (18-MC) on the behavioural and neurochemical responses to chronic cocaine and morphine: Implications for sensitization in the mediation of drug addiction

Karen K. Szumlinski(1)
(1)Albany Medical College - Albany. United States

[ABSTRACT] [INTRODUCTION] [MATERIALS AND METHODS] [RESULTS] [FIGURES] [FIGURES-2] [DISCUSSION] [CONCLUSIONS] [ACKNOWLEDGEMENTS] [REFERENCES] [Discussion Board]
MATERIALS AND METHODS Previous: New bicyclic non-condensited thiazolidones-4 and their cytostatic activity FIGURES
[Neuroscience]
Next: Effects of ethanol on brain aminopeptidase activities under basal and K+-stimulated conditions.
[Pharmacology]
Next: Contraindications to thiazides and beta blockers in hypertense patients treated with nifedipine in five Cuban municipalities.
[Psychiatry]
Next: Augmentation of antidepressant therapy with 5-HT autoreceptor antagonists: receptor autoradiographic studies of pindolol

RESULTS

LOCOMOTOR ACTIVITY

MOR STUDIES: In acute MOR-treated rats, 18-MC (40 mg/kg, 19 h earlier) shifted the dose-response function for locomotion to the left of VEH-pretreated rats - Pretreatment by Dose interaction: F( 6,155 ) = 2.61, P<0.03 - fig. 2. Chronic MOR administration (5 x 20 mg/kg) induced locomotor sensitization in approximately 50% of the rats - Group by Injection Number interaction: F( 4, 368 ) = 5.89, P<0.0005; Group by Injection Number by Time interaction: F( 68,6256 ) = 2.46, P<0.00001 - fig. 3. On test day, this sensitization was apparent in VEH-pretreated rats - Group by Dose interaction: F( 3,39 ) = 3.27, P<0.04 - but not in 18-MC-pretreated rats (40 mg/kg, IP, 19 h earlier) - Group by Dose interaction: P=0.95 - fig. 4.

COC STUDY: Compared to injection 1, sensitization of locomotion was expressed by COC treated animals during chronic treatment - Chronic Treatment by Injection Number interaction: F( 4,368 ) = 4.39, P<0.002 - fig. 5. On test day, compared to chronic SAL rats, a sensitization of locomotion was also observed as indicated by a significant shift to the left in the dose-response function for COC-induced locomotion in chronic COC versus chronic SAL treated rats - Chronic Treatment by Dose interaction: F( 3,38 ) = 2.78, P=0.05 -. In terms of total locomotor responding to COC, 18-MC (40 mg/kg, 19 h earlier) produced a marginal shift to the left in the dose-response curves for COC-induced locomotion - Pretreatment by Dose interaction: F( 3,78 ) = 2.55, P=0.06 - fig. 6. However, 18-MC significantly altered the timecourse of COC-induced locomotion overall - Pretreatment by Dose by Time interaction: F( 33,858 ) = 1.65, P<0.02 - fig.7. This effect depended on the previous COC history of the animal - Chronic Treatment by Pretreatment by Dose by Time interaction: F( 11,858 ) = 1.75, P=0.05 -; 18-MC increased the early locomotor-activating effects of COC in rats with previous COC experience - Pretreatment by Dose by Time interaction: F( 44,1056 ) = 1.35, P=0.06 -, without altering the timecourse of acute COC-induced locomotion - Pretreatment by Dose by Time interaction: F( 44,1056 ) = 1.28, P=0.11 -.

STEREOTYPY

A slight sensitization of stereotypy was observed across injections during chronic COC administration in chronic COC rats - Chronic Treatment by Injection Number interaction: F( 4,184 ) = 8.92, P<0.0001 - fig. 8. In VEH-pretreated rats, repeated COC administration induced a slight sensitization of stereotypy in response to the test injections of COC - Chronic Treatment by Time interaction: F( 9,180 ) = 2.14, P<0.03 - fig. 10. Pretreatment with 18-MC (40 mg/kg, 19 h earlier) potentiated the total amount of stereotypy injected by COC, compared to VEH controls - Pretreatment effect: F( 1,40 ) = 57.00, P<0.0001 - fig. 9. Compared to VEH controls, 18-MC significantly increased the amount of stereotypy expressed in response to 40 mg/kg COC - Pretreatment by Dose interaction: F( 1,40 ) = 5.53, P<0.03 - and marginally prolonged the duration of COCīs stereotypic activating effects - Pretreatment by Time interaction: F( 9,180 ) = 1.86, P=0.06 - fig. 10.

IN VIVO MICRODIALYSIS

MOR STUDY: The average basal concentration of DA or either of its metabolites, DOPAC and HVA, did not differ as a consequence of either chronic MOR treatment or 18-MC pretreatment (data not shown). Compared to injection 1, chronic MOR rats displayed a sensitization of DA release in the NAC on test day. 18-MC (40 mg/kg, 19 h earlier) abolished the DA response to MOR - Group by Time interaction: F( 28,294 ) = 3.4, P<0.0001 - and blocked the MOR-sensitized response of DOPAC - Group by Time interaction: F( 28,294 ) = 1.61, P<0.03 - and HVA - Group by Time interaction: F( 28,294 ) = 1.79, P<0.02 - fig. 11. COC STUDY: The average basal concentration of DA or either of its metabolites, DOPAC and HVA, did not differ as a consequence of either chronic COC treatment or 18-MC pretreatment (data not shown). Compared to SAL rats, chronic COC rats displayed a sensitization of DA levels in the NAC - Chronic Treatment by Time interaction: F( 14,126 ) = 5.52 -. No differences were observed between the two VEH pretreated controls -no main effects or interactions with Chronic Treatment, P>0.05 -. Compared to VEH pretreated animals, 18-MC pretreatment (40 mg/kg, 19 h earlier) differentially altered the DA response in the NAC to COC, depending on the previous COC history of the animal - Chronic Treatment by Pretreatment by Time interaction: F( 14,252 ) = 3.52, P<0.0001 - . 18-MC completely abolished the sensitized DA response to COC - Pretreatment by Time interaction: F( 14,112)4.8, P<0.0001 - fig. 12 . In contrast, 18-MC produced a marginal effect on the DA response in the NAC in chronic SAL rats - Pretreatment by Time interaction: F( 14,140 ) = 1.72, P=0.06 -. Similarly, 18-MC pretreatment differentially altered the DOPAC response to COC, depending on the previous COC history of the animal - Chronic Treatment by Pretreatment by Time interaction: F( 14,266 ) = 1.73, P<0.0001 - fig. 13 . 18-MC pretreatment did not significantly alter the COC-induced changes in extracellular levels of HVA in the NAC - no main effect or interactions with Pretreatment, P>0.05 - fig. 13


Discussion Board
Discussion Board

Any Comment to this presentation?

[ABSTRACT] [INTRODUCTION] [MATERIALS AND METHODS] [RESULTS] [FIGURES] [FIGURES-2] [DISCUSSION] [CONCLUSIONS] [ACKNOWLEDGEMENTS] [REFERENCES] [Discussion Board]

MATERIALS AND METHODS Previous: New bicyclic non-condensited thiazolidones-4 and their cytostatic activity FIGURES
[Neuroscience]
Next: Effects of ethanol on brain aminopeptidase activities under basal and K+-stimulated conditions.
[Pharmacology]
Next: Contraindications to thiazides and beta blockers in hypertense patients treated with nifedipine in five Cuban municipalities.
[Psychiatry]
Next: Augmentation of antidepressant therapy with 5-HT autoreceptor antagonists: receptor autoradiographic studies of pindolol
Karen K. Szumlinski
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Last update: 18/01/00