Differential effects of haloperidol, clozapine, and fluperlapine on tuberoinfundibular dopamine neurons and prolactin secretion in the rat

Abstract

Two atypical neuroleptic agents, clozapine and fluperlapine, produced rapid elevations in plasma PRL concentrations that were similar in magnitude to those produced by haloperidol. However, the PRL response to clozapine or fluperlapine was of much shorter duration than that elicited by haloperidol. Clozapine, but neither fluperlapine nor haloperidol, produced a rapid increase in the activity of tuberoinfundibular dopamine (TIDA) neurons, as evidenced by an enhanced accumulation of dihydroxyphenylalanine (DOPA) in the median eminence after the inhibition of DOPA decarboxylase. The clozapine-induced increase in DOPA accumulation was evident within 30 minutes after its administration and persisted for at least 4 hours. The clozapine-induced increase in the activity of TIDA neurons may account, in part, for the abbreviated PRL response to this neuroleptic. In addition, ability to produce a short-lived increase in PRL secretion in the rat appears to be common to the atypical neuroleptic drugs.

Correlated Changes in Symptoms and Neurotransmitter Indices during Maintenance Treatment with Clozapine or Conventional Neuroleptics in Adolescents and Young Adults with Schizophrenia

“…Clozapine did not increase plasma prolactin levels in our adolescent sample during maintenance treatment, consistent with clinical data and animal studies (Ackenheil 1989, Albinsson et al 1993, Gudelsky et al 1987, Lieberman et al 1986, Meltzer 1989, 1992b. Basal prolactin secretion is under inhibitory dopaminergic control but is stimulated by serotonin agonists (Meltzer 1992a,b).…”

Effects of the atypical antipsychotics olanzapine and risperidone on plasma prolactin levels in male rats: a comparison with clinical data

“…Clinically, several studies have demonstrated elevations of prolactin on initial treatment with antipsychotics (Hamner 2002;Crawford et al 1997;Goff et al 1998;Gudelsky et al 1987). Olanzapine was found to produce moderate increases in prolactin levels in the acute phase of treatment (6 weeks), whilst risperidone has been associated with 30-300% increases over the same period (Breier et al 1999;David et al 2000).…”

Use of neuroendocrine effects in discrimination between CNS‐active drugs in the rat

“…This shortlasting increase of prolactin is most probably a result of the ability of the atypical antipsychotics to stimulate the TIDA neurons [Gudelsky et al, 19871. In contrast typical antipsychotic drugs do not influence the activity in the TIDA neurons [Gudelsky et al, 1987;Gudelsky and Meltzer, 19891. Atypical antipsychotics are more potent stimulators of the hypothalamic-pituitary-adrenocortical axis than typical antipsychotic drugs because of an elevated serotonergic nerve activity induced by the atypical ones "ash et al, 19881.…”