K F Melia

Harvard Medical School, Boston, MA, United States

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Publications (3)10.44 Total impact

  • Neurochemistry International 04/1992; 20 Suppl:147S-152S. · 2.66 Impact Factor
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    ABSTRACT: The involvement of dopamine (DA) receptor subtypes in the discriminative stimulus effects of cocaine was investigated in squirrel monkeys trained to discriminate cocaine from vehicle using a two-lever choice procedure. Lever pressing was maintained under a 10-response fixed-ratio schedule of food presentation. In substitution tests, (-)-cocaine and its high-affinity analogs 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (CFT) and 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)tropane (CCT) engendered dose-related increases in the proportion of cocaine-appropriate responses. Full (97-100%) substitution for the training dose of cocaine was observed with all three drugs, the rank order of potency being: CCT greater than CFT greater than cocaine. DA agonists differing in selectivity for D1 and D2 receptor subtypes [6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-[1H]-3-benzazepine (SKF 81297), 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-3-allyl-[1H]-3- benzazepine (SKF 82958), (+)-4-propyl-9-hydroxynapthoxazine [(+)-PHNO], quinpirole, quinelorane, (-)-4,6,6a,7,8,-12b-hexahydro-7-methyl-indolo[4,3-ab]phen ant hridine (CY 208-243) and (-)-apomorphine] also engendered dose-related increases in cocaine-appropriate responses. However, maximally effective doses of these drugs occasioned an average of only 54 to 77% responses on the cocaine-associated lever and markedly reduced response rates. Combinations of the D1 agonist SKF 81297 and the D2 agonist (+)-PHNO did not engender a consistently higher proportion of cocaine-appropriate responses than did either drug alone.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of Pharmacology and Experimental Therapeutics 10/1991; 258(3):945-53. · 3.89 Impact Factor
  • K F Melia, R D Spealman
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    ABSTRACT: Squirrel monkeys were trained to discriminate the selective dopamine uptake inhibitor GBR 12909 (1-[2-[bis(4-fluorophenyl)-methoxy] ethyl]-4-(3-phenylpropyl)piperazine) from saline in a two-lever drug-discrimination procedure. After i.v. injections of GBR 12909, 10 consecutive responses on one lever produced food, whereas after i.v. saline, 10 consecutive responses on the other lever produced food. By using a cumulative-dosing procedure, several inhibitors of monoamine uptake as well as dopamine receptor agonists and antagonists were evaluated for their ability to substitute for, or attenuate, the discriminative-stimulus effects of GBR 12909. Dopamine uptake inhibitors, including GBR 12909, cocaine, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane, mazindol, bupropion and methylphenidate, as well as the dopamine releasing drug (+)-amphetamine substituted fully (greater than 80% drug-lever responding) for the training dose of GBR 12909. In contrast, the selective norepinephrine uptake inhibitors, desipramine and talsupram, and the selective serotonin uptake inhibitor, citalopram, occasioned averages of only 13 to 19% drug-lever responding. The dopamine D1 agonist SKF 81297 (6-chloro-7,8-ddhydroxy-1-phenyl-2,3,4,5-tetrahydro-[1H]-3- benzazepine), the D2 agonists, (+)-4-propyl-9-hydroxynaphthoxazine and quinpirole, and the nonselective dopamine agonist, (-)-apomorphine, all occasioned a majority of responses (mean = 56-82%) on the drug-appropriate lever. The D1 partial agonists, R-SKF 38393 (R-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro- [1H]-3-benzazepine) and SKF 75670 (7,8-dihydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-[1H]-3-benzazepine), however, occasioned an average of no more than 21% drug-appropriate responding.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of Pharmacology and Experimental Therapeutics 09/1991; 258(2):626-32. · 3.89 Impact Factor