Changes in Cortical 5-HT₂ Receptors Following 5-HTP and Paroxetine Administration in Rats

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Rats were pretreated with either carbidopa (25 mg/kg 30 min previously) or phenelzine (50 mg/kg 18 h and 12 mg/kg 90 min previously) before being given 5-HTP (150 or 350 mg/kg) or paroxetine (12 mg/kg). In carbidopa-treated animals, 5-HTP (150 mg/kg) evoked many wet-dog shakes (WDS) without changing receptor numbers, but an increase in the dose of 5-HTP to 350 mg/kg paradoxically increased the number of cortical 5-HT₂ receptors. The increase was reversed by pretreating the rats with haloperidol (5 mg/kg), but this did not occur withα-methyl-para-tyrosine (250 mg/kg 16 h and 4 h before carbidopa). Apomorphine (2 mg/kg) in phenelzine-treated rats and apomorphine (10 mg/kg) in untreated rats increased 5-HT₂ receptor numbers. The reason for the failure of 5-HTP to rapidly down-regulate 5-HT₂ receptors is not known, but is thought to depend in some complex way on the proportion of 5-HTP that is decarboxylated to 5-HT outside serotonergic neurons, thus affecting the dopaminergic mechanism. In phenelzine-treated rats, paroxetine produced a 5-HT-dependent syndrome, which included WDS, and a significant reduction in cortical 5-HT₂ receptors within 3 h. WDS were unaffected by administration of propranolol (20 mg/kg) or pindolol (5 mg/kg), confirming that WDS were independent of 5-HT_1A receptors. The reduction of 5-HT₂ receptors was not associated with migration of the receptors into the “light-density fraction” of the cortex, isolated by density-gradient centrifugation.