The partial D2-like dopamine receptor agonist terguride acts as a functional antagonist in states of high and low dopaminergic tone: evidence from preweanling rats.
BACKGROUND
In adult rats, the partial D(2)-like agonist terguride acts as an antagonist at normosensitive D(2)-like post-synaptic receptors, while it acts as an agonist at the same receptors during states of low dopaminergic tone.


OBJECTIVE
The purpose of the present study was to determine whether partial D(2)-like agonists exhibit both antagonistic and agonistic actions during the preweanling period.


METHODS
In experiments 1 and 2 (examining the agonistic actions of terguride), preweanling rats were either given an escalating regimen of amphetamine to induce a state of amphetamine withdrawal or pretreated with the tyrosine hydroxylase inhibitor AMPT. Distance traveled was measured after rats were injected with saline, terguride (0.4-1.6 mg/kg), or the full D(2)-like receptor agonist NPA (0.01 mg/kg). In experiment 3 (examining the antagonistic actions of terguride), preweanling rats were pretreated with terguride 30 min before they were tested with saline, NPA (0.05 mg/kg), or amphetamine (1.5 mg/kg).


RESULTS
NPA had an exaggerated locomotor activating effect when tested under conditions of amphetamine withdrawal, while the partial D(2)-like agonist did not enhance distance traveled under any circumstance. Similarly, NPA increased and terguride did not affect the distance-traveled scores of AMPT-pretreated rats. In experiment 3, terguride pretreatment significantly reduced the distance traveled of amphetamine-treated and NPA-treated rats.


CONCLUSIONS
The behavioral evidence indicates that, during the preweanling period, terguride antagonizes D(2)-like post-synaptic receptors in a state of high dopaminergic tone; however, there is no evidence that terguride is capable of stimulating D(2)-like post-synaptic receptors during states of low dopaminergic tone.
McDougall
Sanders A
SA
Department of Psychology, California State University, San Bernardino, CA, 92407, USA. smcdouga@csusb.edu
Hernandez
Rita M
RM
Reichel
Carmela M
CM
Farley
Cristal M
CM
D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D006948:Hyperkinesis / Q000139:chemically induced; D008090:Lisuride / Q000031:analogs & derivatives* / Q000494:pharmacology; D008781:Methyltyrosines / Q000008:administration & dosage / Q000493:pharmacokinetics; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000008:administration & dosage* / Q000819:agonists*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D008781:Methyltyrosines; D017448:Receptors, Dopamine D2; C006208:dironyl; C022260:alpha-methyltyrosine methyl ester; D008090:Lisuride; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine