On spinal noradrenaline receptor supersensitivity: correlation between nerve terminal densities and flexor reflexes various times after intracisternal 6-hydroxydopamine.
The noradrenaline (NA)-dependent hindlimb flexor reflex that can be elicited by pinching the foot of acutely spinalized rats given nialamide-DOPA or clonidine was evaluated different time intervals (14 days-6 months) after intracisternal injections of 6-OH-dopamine (6-OH-DA) and correlated to the degree of bulbospinal catecholamine (CA) denervation as seen by Falck-Hillarp fluorescence histochemistry. Six and 14 days after 6-OH-DA, when almost all NA nerve terminals of the spinal cord had degenerated, the NA receptors where supersensitive to stimulation with clonidine as evidenced by an increased flexor reflex. This supersensitivity gradually disappeared as new nerve terminals were formed in the grey matter of the spinal cord during the following 3-6 months. The supersensitivity phenomenon 14 days after 6-OH-DA could also be demonstrated by L-DOPA given to animals pretreated with 100 mg/kg nialamide. Using this relatively low dose of nialamide, almost no reflex response was seen in the control group. Using a higher degree of monoaminoxidase inhibition (nialamide 200 mg/kg) also non-supersensitive, NA receptors became maximally stimulated. Therefore, 6-OH-DA treated rats now showed a weaker reflex than controls, the reflex response being directly correlated to the number of nerve terminals present that could form NA from the precursor. Using 5,6-dihydroxytryptamine, which selectively destroys 5-hydroxytryptamine (5-HT) nerves, it was shown that the flexor reflex changes were specifically related to the NA nerves and unchanged by the simultaneous presence or absence of 5-HT nerve terminals. This was further supported by the finding of a correlation between amount of nerve terminals and flexor reflex responses in individual animals, especially at longer survival times both in the clonidine and the nialamide-DOPA experiments.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001835:Body Weight; D002452:Cell Count; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb; D006892:Hydroxydopamines / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009411:Nerve Endings / Q000166:cytology / Q000187:drug effects*; D009526:Nialamide / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects*; D013997:Time Factors
D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D012701:Serotonin; D007980:Levodopa; D003000:Clonidine; D001058:Apomorphine; D009526:Nialamide