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The dopamine receptor antagonist SCH 23390 attenuates feeding induced by 9tetrahydrocannabinol

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Is there an interaction between the Cannabinoid and Dopamine systems for food regulation? ... Hind part of body carefully lifted until abdomen visible ... – PowerPoint PPT presentation

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Title: The dopamine receptor antagonist SCH 23390 attenuates feeding induced by 9tetrahydrocannabinol


1
The dopamine receptor antagonist SCH 23390
attenuates feeding induced by ?9-tetrahydrocannabi
nol
  • Prepared by Michael Sonta

2
Is there an interaction between the Cannabinoid
and Dopamine systems for food regulation?
  • The Cannabinoid system
  • The Dopamine system
  • Intraperitoneal Drug Administration
  • The Eperiments
  • Results/Findings
  • Implications/Contributions to Science
  • Questions

3
The Cannabinoid system
  • CB1 Receptors
  • Primary CNS
  • Cerebellum, Cerebral cortex, Medulla, Basal
    ganglia, Nucleus accumbens, and Hypothalamus
  • CB2 Receptors
  • Peripheral tissues and immune system

4
Endogenous Cannabinoid system
  • Increased responses from leptin (Adipose tissues,
    Neuropeptide Y)
  • Decrease in endogenous cannabinoids (anandamide)
  • Decrease Appetite

5
Endogenous Cannabinoid system
  • Decreased Leptin responses
  • Increase in endogenous cannabinoids
  • Increased Appetite

6
Exogenous Cannabinoid system
  • Increased ?9-THC
  • Increased Appetite

7
The Dopamine system
  • Involved in pleasure and reward
  • 6-OHDA lesions of nigrostriatal dopaminergic
    pathway lead to aphagia
  • DA D1-like receptor antagonists reduce food
    intake

8
3 Experiments
  • Albino Wistar rats, 8-10 weeks old
  • 8 rats for exp. 1 and 8 for exp. 2
  • For exp. 3, the rats were combined
  • 12-h12-h light-dark cycle
  • Access to rat chow and water
  • Locomotor activity was monitored using an
    infrared detector (sec)
  • Food consumption was measured in weight (g)
  • Intraperitoneal Drug Administration

9
Intraperitoneal Drug Administration
  • Intraperitoneal means the administration of drug
    through the peritoneum.
  • The peritoneum is a thin, transparent membrane
    lining the walls of the abdominal (peritoneal)
    cavity.

10
Intraperitoneal Drug Administration
  • Rat is fixed with a cloth covering body
  • Thumb placed on caudal side of tail
  • Rest of hand placed cranially from the tail,
    which fixes the rat in place

11
Intraperitoneal Drug Administration
  • Hind part of body carefully lifted until abdomen
    visible
  • Rats back must be bent carefully or damage,
    pain, or resistance may occur

12
Intraperitoneal Drug Administration
  • Intraperitoneal injection with right hand
  • Injection lateral from the linea alba at a
    horizontal level between the knees
  • 1ml/kg body weight

13
Experiment 1 Effects of SCH 23390 on feeding
  • Rats (n8) injected with either DH20 or SCH 23390
    every 24 hrs
  • Tested every 48 hrs
  • On the first day all rats (n8) received a
    habituation session
  • Injected with DH2O (1ml/kg) only
  • Rats injected with SCH 23390 received doses of
    0.005, 0.01, 0.05 or 0.1 mg/kg

14
Experiment 1 Effects of SCH 23390 on feeding
results
  • SCH 23390 attenuated food intake in a dose
    dependent manner
  • Locomotor activity was significantly decreased

15
Experiment 2 Effects of ?9-THC on feeding
  • Rats (n8) injected with either vehicle or ?9-THC
    every 24 hrs
  • Tested every 48 hrs
  • On the first day all rats (n8) received a
    habituation session
  • Injected with vehicle (1ml/kg) only
  • Satiation phase
  • Rats injected with ?9-THC received doses of 0.1,
    0.5 or 1.0 mg/kg

16
Experiment 2 Effects of ?9-THC on feeding results
  • ?9-THC stimulated food intake in a dose dependent
    manner
  • Locomotor was different than vehicle (biphasic
    effect)

17
Experiment 2 Effects of SCH 23390 on ?9-THC
induced feeding
  • Rats (n16) injected with DH2O or SCH 23390
    (0.005, 0.01, 0.05 or 0.1 mg/kg) followed 25 min
    later by vehicle or ?9-THC (1.0 mg/kg) every 24
    hrs
  • Tested every 48 hrs
  • On the first day all rats (n16) received a
    habituation session
  • Injected with vehicle (1ml/kg) only
  • Satiation phase

18
Experiment 2 Effects of SCH 23390 on ?9-THC
induced feeding results
  • Food eaten was affected by SCH 23390 dosage
  • Dosage had no effect on locomotor activity

19
Results/Findings
  • The Dopamine system is involved in cannabinoid
    food intake (SCH 23390 attenuates eating)
  • SCH 23390 produced a dose dependent suppression
    of locomotor activity (exp 1) suggesting that a
    reduction in food intake may have been due to a
    general reduction in motivated behaviour
  • 0.1 mg/kg of SCH 23390 (exp 1)and 1.0 mg/kg of
    ?9-THC reduced locomotor activity when
    administered alone, but when combined had no
    effect on locomotor activity
  • Interactions may be mediated in the NAC
  • NAC plays an important role in food and incentive
    learning
  • NAC links cortical systems and hypothalamic
    feeding info.
  • Interactions may also occur in the
    gastrointestinal tract

20
Implications/Contributions to Science
  • Cancer and AIDS patients
  • Anorexia Nervosa
  • Obesity

21
Questions
  • Which brain regions mediate the interaction
    between the cannabinoid and dopamine systems?
  • Could interactions between these systems occur
    elsewhere, other than the brain?
  • What is Intraperitoneal Drug Administration? And,
    which muscle group must be avoided during
    injection?
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