Involvement of mesolimbic and extrapyramidal nuclei in the motor depressant action of narcotic drugs
- 1 September 1978
- journal article
- Published by Oxford University Press (OUP) in Journal of Pharmacy and Pharmacology
- Vol. 30 (1), 566-572
- https://doi.org/10.1111/j.2042-7158.1978.tb13325.x
Abstract
The ability of narcotic drugs to induce motor depression from the mesolimbic nucleus accumbens (ACB) and extrapyramidal caudate-putamen (CP) was investigated using the bilateral intracerebral injection technique. Fluphenazine and procaine were used as control agents. Firstly, drugs were injected alone into the ACB or CP and catalepsy was assessed. Fentanyl (2·5–10μg), sufentanil (0·25–1 μg) and carfentanil (0·05–0·5μg) were shown to be potent cataleptogens when injected into both the ACB and CP, the responses being dose-dependent and achieving maximum intensity. Morphine (1–50 μg) also induced a marked dose-dependent catalepsy, but only after injection into the ACB. In contrast, pethidine and methadone, in doses up to 160 μg, caused only weak and inconsistent responses from the ACB and CP. Similar injections of procaine (50–200 μg) were ineffective, but fluphenazine (25–200 μg) induced a moderate dose-dependent response from both the ACB and CP, although onset of action was more rapid and the duration markedly longer for the latter injections. Secondly, drugs were injected peripherally and intracerebrally to determine their ability to antagonize the marked hyperactivity induced by intra-ACB dopamine in the presence of nialamide. Two agents shown to induce catalepsy from the ACB, fluphenazine and morphine, antagonized dopamine hyperactivity when they were administered peripherally or directly into the ACB (0·1–0·2 mg kg−1, i.p. or 3·1–25 μg fluphenazine and 1–5 mg−1 kg, s.c. or 1–5 μg morphine), but only a weak antagonism occurred at much larger doses after intra-CP injections (100 μg fluphenazine and 50 μg morphine). Larger doses of intra-ACB pethidine (160 μg) and procaine (100–200 μg) also antagonized the dopamine response, but methadone was inactive. Again, the most potent and effective drugs in this test were fentanyl (1–5 μg), sufentanil (0·25–0·5μg) and carfentanil (0·05–0·1 μg). It is suggested that the ACB, and not the CP, is the site at which morphine acts to cause motor depression, whilst other narcotic drugs are able to act in both areas (although there is some indication of a further unspecified site of action for methadone). In contrast, the neuroleptic fluphenazine appears to differentially affect motor function via the ACB and CP, antagonizing a dopamine hyperactivity in the former and primarily inducing catalepsy from the latter nucleus.Keywords
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