title: Long-term amphetamine treatment attenuates or reverses the depression of neuronal activity produced by dopamine agonists in the ventral tegmental area.
abstract: Neuronal activity was recorded from the ventral tegmental area (VTA) of immobilized, locally anesthetized rats on the day immediately following long-term treatment (twice daily for 6 consecutive days) with saline, 1.0 or 5.0 mg/kg d-amphetamine (d-AMPH). Each rat was challenged intravenously with d-AMPH (beginning with 0.0625 mg/kg) or with 0.005 mg/kg apomorphine. Treatment with d-AMPH significantly reduced the ability of this drug to inhibit VTA activity. In fact, nearly half of the neurons in the high-dose treatment group were excited by d-AMPH, whereas only 20% of control neurons showed this response. Moreover, apomorphine routinely accelerated firing rate in the VTA following treatment with 5.0 mg/kg d-AMPH but this response was never observed in control neurons, not even in those that were excited by d-AMPH. Thus, tolerance appears to develop to the ability of dopamine agonists to inhibit VTA activity and this effect may be mediated, at least in part, by a subsensitivity of inhibitory dopamine autoreceptors.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D004361:Drug Tolerance; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D006220:Haloperidol; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine