Title: The dopamine receptor antagonist SCH 23390 attenuates feeding induced by 9tetrahydrocannabinol
1The dopamine receptor antagonist SCH 23390
attenuates feeding induced by ?9-tetrahydrocannabi
nol
- Prepared by Michael Sonta
2Is 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
3The Cannabinoid system
- CB1 Receptors
- Primary CNS
- Cerebellum, Cerebral cortex, Medulla, Basal
ganglia, Nucleus accumbens, and Hypothalamus
- CB2 Receptors
- Peripheral tissues and immune system
4Endogenous Cannabinoid system
- Increased responses from leptin (Adipose tissues,
Neuropeptide Y) - Decrease in endogenous cannabinoids (anandamide)
- Decrease Appetite
5Endogenous Cannabinoid system
- Decreased Leptin responses
- Increase in endogenous cannabinoids
- Increased Appetite
6Exogenous Cannabinoid system
- Increased ?9-THC
- Increased Appetite
7The 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
83 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
9Intraperitoneal 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.
10Intraperitoneal 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
11Intraperitoneal Drug Administration
- Hind part of body carefully lifted until abdomen
visible - Rats back must be bent carefully or damage,
pain, or resistance may occur
12Intraperitoneal Drug Administration
- Intraperitoneal injection with right hand
- Injection lateral from the linea alba at a
horizontal level between the knees - 1ml/kg body weight
13Experiment 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
14Experiment 1 Effects of SCH 23390 on feeding
results
- SCH 23390 attenuated food intake in a dose
dependent manner - Locomotor activity was significantly decreased
15Experiment 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
16Experiment 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)
17Experiment 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
18Experiment 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
19Results/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
20Implications/Contributions to Science
- Cancer and AIDS patients
- Anorexia Nervosa
- Obesity
21Questions
- 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?