ISSN:
1432-1912
Keywords:
Key words: Haloperidol – Ventral tegmental area – Substantia nigra – Nucleus accumbens – Striatum
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract. Most antipsychotic drugs are, in addition to being dopamine (DA) D2 receptor antagonists, also relatively potent α1 adrenoceptor antagonists. Here, we have studied the effects of the selective DA D2 receptor antagonist raclopride, alone and in combination with the selective α1 adrenoceptor antagonist, prazosin, on midbrain DA neurons utilizing extracellular single cell recording techniques. As a reference compound, haloperidol (0.05–1.6 mg/kg, i.v.), a potent antagonist at both DA D2 receptors and α1 adrenoceptors, was included in the electrophysiological part of the study. In addition, in vivo voltammetry was used to measure extracellular DA concentrations in the nucleus accumbens (NAC) and the dorsolateral striatum (STR) in anesthetized, pargyline pretreated rats treated with the above drugs. Raclopride (10–5120 μg/kg, i.v.) induced a dose dependent increase in firing rate of DA neurons in the ventral tegmental area (VTA), that was significant already at 10 μg/kg, and in the substantia nigra-zone compacta (SN-ZC), that reached significance at 2560 μg/kg. Burst firing of DA neurons was also increased in the VTA at 40 μg/kg, as well as in the SN-ZC at 640 μg/kg. A low dose of raclopride (80 μg/kg, cumulated dose) induced a significant increase in extracellular DA concentrations in NAC to 490% and in STR to 220%. A high dose of raclopride (2560 μg/kg, cumulated dose) induced a 930% increase in extracellular DA concentrations in NAC, but only a 280% increase in STR. These data demonstrate that raclopride exerts a relatively selective action on mesolimbic DA neurons. Prazosin (0.3 mg/kg, i.v.) decreased burst firing of VTA, but not SN-ZC DA neurons. Pretreatment with prazosin (15 min) significantly enhanced the increase in firing rate of VTA-DA neurons caused by raclopride within the 20–160 μg/kg dose range. The effects of the pretreatment on raclopride-induced burst firing, on the other hand, was a marked decrease in VTA-DA neurons, while it left the effect of raclopride on SN-ZC DA neurons unaffected. Pretreatment with prazosin also caused a reduction in the raclopride-induced elevation of extracellular DA concentrations in the NAC, but not in the STR. This effect was only seen with the high dose of raclopride (2560 μg/kg). Although haloperidol increased both firing rate and burst firing of neurons in VTA and SN-ZC, the haloperidol-induced increase in burst firing appeared much smaller than that caused by raclopride. Thus, α1 adrenoceptors seem to modulate the effects of DA D2 receptor antagonism preferentially in the mesolimbic DA system.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00169289
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