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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]
INTRODUCTION Previous: New bicyclic non-condensited thiazolidones-4 and their cytostatic activity RESULTS
[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

MATERIALS AND METHODS

LOCOMOTOR ACTIVITY

MOR STUDIES: The effects of pretreatment with 18-MC on MOR-induced locomotor activation were determined in two separate studies, one for acute MOR, the other for chronic MOR. In the acute MOR study, female Sprague-Dawley rats were pretreated with either 18-MC (40 mg/kg) or vehicle (VEH). Nineteen hours later, rats were randomly addigned to received one of seven test doses of MOR (0, 0.05, 0.125, 5, 10, 20 or 30 mg/kg, IP; n=8-14). In the chronic MOR study, rats were administered five daily injections of 20 mg/kg MOR. Following 3 days of withdrawal, animals were pretreated with either 18-MC (40 mg/kg, IP) or VEH and then, 19 h later, were injected with one of four test doses of MOR (0, 5, 10, and 30 mg/kg, IP; n=5-7). Upon completion of the four test doses of MOR (0, 5, 10, and 30 mg/kg, IP; n=5-7). Upon completion of the experiment, rats were designated "sensitized" or "non-sensitization" by an experiment blind to the pretreatment of the animals, based on whether or not the latency to onset of locomotor activation advanced from injection 1 to injection 5 of chronic treatment. In both studies, rats were immediately placed into automated activity monitors after MOR injection, where their locomotor activaty was recroded for 3 h.

COC STUDY: The effects of pretreatment with 18-MC on COC-locomotor activation were determined. Animals were treated in a similar manner as those in the chronic MOR experiment with the following exceptions: 1) for chronic treatment, rats were administered five daily injections of either 15 mg/kg COC or SAL, followed by 2 weeks withdrawal; 2) the COC test doses employed were 0, 10, 20 and 40 mg/kg, IP; and 3) locomotor activity was monitored for 2 h and all COC injection sessions were preceded by a 30 min SAL habituation session.

STEREOTYPY

The effects of pretreatment (40 mg/kg, IP, 19 h earlier) with 18-MC on COC-induced stereotypy were determined. Identical procedures were followed for chronic COC treatment and 18-Mc pretreatment as descrived for the COC locomotor study above. Stereotypy was monitored for 2 or 3 h (chronic treatment and test days, respectively) in clear, cylindrical cages and rated every 20 min by an experimenter blind to the pretreatment of the animals, according to procedures described in Kalivas et al. (7).

IN VIVO MICRODIALYSIS

MOR STUDY: Female Sprague-Dawley rats were stereotaxically implanted with guide cannulae aimed bilaterally at the NAC (AP, + 1.6 mm and L, +/- 1.3 mm with respect to bregmal; V, -4.6 mm, at an angle of 14 degrees). Four days later, rats were placed in a cylindrical chamber with free access to food and water and a dialysis probe (CMA/Microdialysis probes: 2mm) was inserted unilaterally. Artificial CSF containing 146 mM NaCl, 2.7 mM KCl, 1.2 CaCl2 and 1.0 mM MgCl2 was delivered at a flow rate of 1 µl/min. Collection of perfusates began the next day and consisted of a 2-h baseline session, MOR injection (20 mg/kg, IP) and then a 3-h test session. Upon completion of injection 1, the dialysis probe was removed. Rats then received 4 addiction, once daily, MOR injections (20 mg/kg) in their home cages which were placed in the experimental room for 3 h. Following 2 days of withdrawal, animals were randomly addigned to receive either 18-MC (40 mg/kg, IP) or VEH, such that pretreatment occurred exactly 19 h prior to MOR administration the next day. Cannulae were inserted unilaterally on the opposite side of the head than that used for injection 1. The next day, perfusate collection and MOR injection occurred as described for injection 1 above. Analysis of the smaples are described below.

COC STUDY: Female rats were implanted with guide cannulae as described above. For chronic treatment, rats received five, once daily, injections of 15 mg/kg COC (as described for the study of COC locomotion) in their home cages, which were placed in the experimental room for 3 h. Chronic COC treatment began the day following surgery. Following 2 weeks withdrawal, 2 probes were inserted bilaterally into the NAC, and testing occurred as described above with the exception that 20 mg/kg COC was administered as the test dose. For both MOR and COC studies, upon completion of an experiment, the locations of the probe tips were verified according to the altlas of Paxinos and Watson (1986). Dialysate samples were assayed for DA, DOPAC and HVA by HPLC with electrochemical detection (ESA Coulochem detector). Chromatograms were integrated, compared to standards and analyzed using Hewlett Packard ChemStation software.


Discussion Board
Discussion Board

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

INTRODUCTION Previous: New bicyclic non-condensited thiazolidones-4 and their cytostatic activity RESULTS
[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