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Intraamygdaloid morphine produces seizures and brain damage in rats
Abstract:
Behavioral and neuropathological responses to increasing doses of morphine hydrochloride (10-75 micrograms) administered into the rat amygdala were studied. Unilateral microinjections of morphine in doses of 40 and 75 micrograms produced a sequence of behavioral alterations including staring spells, gustatory automatisms, wet dog shakes, motor limbic seizures and limbic status epilepticus. Lower doses of morphine (10 and 20 micrograms) showed different threshold for these behavioral phenomena but a similar time course of development. Histological examination of frontal forebrain sections revealed widespread, apparently seizure-mediated pattern of brain damage. Neuropathological alterations were observed in the olfactory cortex, thalamus, neocortex, hippocampal formation and amygdaloid complex. Pretreatment of animals with diazepam (10 mg/kg i.p.) prevented the development of sustained limbic seizures and brain damage caused by morphine, while pretreatment with naloxone hydrochloride (2-20 mg/kg i.p.) failed to affect morphine-induced convulsant activity and brain damage. These results may suggest that morphine elaborates sustained limbic seizures and widespread brain damage by mechanism underlying the antagonism of inhibitory amino acid neurotransmission and opioid receptors do not seem to be involved.
Insights
Morphine administration into the rat amygdala caused seizures and brain damage. Diazepam prevented these effects, suggesting morphine
Area of Science:
- Neuroscience
- Pharmacology
- Neuropathology
Background:
- The amygdala's role in behavioral and neuropathological responses is complex.
- Morphine's effects on the central nervous system require further elucidation.
Purpose of the Study:
- To investigate the behavioral and neuropathological consequences of escalating morphine hydrochloride doses in the rat amygdala.
- To explore the involvement of opioid receptors and inhibitory neurotransmission in morphine-induced effects.
Main Methods:
- Unilateral microinjections of varying morphine hydrochloride doses (10-75 micrograms) into the rat amygdala.
- Observation of behavioral alterations and induction of limbic seizures.
- Histological examination of brain sections to identify neuropathological damage.
- Pretreatment with diazepam and naloxone hydrochloride to assess their modulatory effects.
Main Results:
- Morphine doses of 40 and 75 micrograms induced staring spells, gustatory automatisms, wet dog shakes, motor limbic seizures, and limbic status epilepticus.
- Lower morphine doses exhibited varied thresholds but similar time courses for behavioral changes.
- Histological analysis revealed widespread, seizure-mediated brain damage in the olfactory cortex, thalamus, neocortex, hippocampal formation, and amygdaloid complex.
- Diazepam pretreatment blocked morphine-induced seizures and brain damage, while naloxone hydrochloride did not.
Conclusions:
- Morphine induces sustained limbic seizures and brain damage in rats, potentially via antagonism of inhibitory amino acid neurotransmission.
- Opioid receptors do not appear to be directly involved in mediating these morphine-induced effects.
- Diazepam's protective action suggests a role for GABAergic mechanisms in mitigating morphine's neurotoxic effects.