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Plasma catecholamine and cardiovascular responses to morphine and D-ala2-d-leu5-enkephalin in conscious rats
Abstract:
The effects of morphine and DADL on cardiovascular parameters and plasma catecholamine levels were studied in conscious unrestrained rats. Morphine 30 micrograms icv increased blood pressure over the 3 hr recording period, produced an initial bradycardia followed by a tachycardia and increased plasma epinephrine and norepinephrine levels 20- and 2-fold respectively. These responses were not altered by systemic naloxone 0.8 mg/kg ia or naloxone injected icv 110 micrograms. In adrenalectomized rats blood pressure, heart rate and plasma norepinephrine responses were not significantly altered. Lower doses of morphine 1, 3 and 10 micrograms icv produced dose-related increases in plasma catecholamines, in the absence of any signs of respiratory depression, which were antagonized by naloxone 110 micrograms icv. 1m Morphine 10 mg/kg produced effects similar to those of icv morphine and these were readily antagonized by naloxone 0.8 mg/kg ia. DADL 10 micrograms icv also produced effects similar to those of morphine but of a shorter duration, and these were also inhibited by naloxone 0.8 mg/kg ia. The results are consistent with an action of opiates on a specific opiate receptor in the brain mediating an increase in catecholamine release. The rise in blood pressure may in part be a consequence of the increase in circulating catecholamines.
Insights
Opiate drugs like morphine and DADL increase cardiovascular activity and plasma catecholamines in rats by acting on brain opiate receptors. Naloxone, an opiate antagonist, blocks these effects, suggesting a central mechanism.
Area of Science:
- Pharmacology
- Neuroscience
- Cardiovascular Physiology
Background:
- Opiates are known to affect cardiovascular function and neuroendocrine responses.
- The precise central mechanisms underlying these effects, particularly concerning catecholamine release, require further elucidation.
Purpose of the Study:
- To investigate the effects of intracerebroventricular (ICV) administration of morphine and DADL on cardiovascular parameters and plasma catecholamine levels in conscious rats.
- To determine the role of central and peripheral opiate receptors in mediating these responses using naloxone antagonism and adrenalectomy.
Main Methods:
- Conscious, unrestrained rats were administered morphine and DADL via ICV injection or intravenous (IV) administration.
- Cardiovascular parameters (blood pressure, heart rate) and plasma catecholamine (epinephrine, norepinephrine) levels were measured.
- The effects were assessed in the presence and absence of systemic or ICV naloxone, and in adrenalectomized rats.
Main Results:
- ICV morphine (30 µg) increased blood pressure, altered heart rate, and elevated plasma epinephrine and norepinephrine levels.
- These effects of higher dose morphine were not antagonized by systemic or ICV naloxone, nor significantly altered in adrenalectomized rats.
- Lower doses of ICV morphine (1-10 µg) produced dose-dependent increases in plasma catecholamines, antagonized by ICV naloxone, without respiratory depression.
- Intravenous morphine (10 mg/kg) and ICV DADL (10 µg) mimicked morphine's effects and were antagonized by naloxone.
Conclusions:
- Opiates act on specific central opiate receptors to increase catecholamine release.
- The observed rise in blood pressure may be partly mediated by increased circulating catecholamines.
- These findings highlight a central mechanism for opiate-induced cardiovascular and sympathoadrenal activation.