Effects of B-HT 920 on nigrostriatal and mesolimbic dopamine systems in normosensitive and supersensitive rats

Br J Pharmacol. 1990 Mar;99(3):509-15. doi: 10.1111/j.1476-5381.1990.tb12959.x.

Abstract

1. B-HT 920, a D2 dopamine receptor agonist, was tested for its ability to exert presynaptic actions in normosensitive rats, and for possible postsynaptic actions in rats made 'supersensitive' to apomorphine. 2. In normosensitive rats, B-HT 920 (0.01-0.3 mg kg-1, i.p.) increased dopamine concentrations and lowered metabolite levels to a similar extent in all four terminal regions examined (medial prefrontal cortex, olfactory tubercle, nucleus accumbens, caudate-putamen). Analogous effects were seen for 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid. 3. Rats which received bilateral 6-hydroxydopamine (6-OHDA) infusions into the caudate-putamen showed signs of postsynaptic dopamine receptor activation (stereotyped behaviour) in response to B-HT 920 (0.1 and 1.0 mg kg-1, i.p.) and to apomorphine (0.2 mg kg-1, s.c.). Similarly, B-HT 920 (0.1 mg kg-1) induced contralateral circling in rats that had received unilateral 6-OHDA infusions into the medial forebrain bundle; the rate of circling increased gradually over several weeks. 4. In contrast, bilateral 6-OHDA infusions into the nucleus accumbens resulted in a supersensitive (locomotor stimulant) response to a low dose of apomorphine (0.1 mg kg-1, s.c.), but not to B-HT 920 (0.01 and 0.1 mg kg-1). 5. In intact rats, withdrawal of chronic haloperidol treatment induced behavioural supersensitivity to apomorphine but not to B-HT 920.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Azepines / pharmacology*
  • Biogenic Monoamines / metabolism
  • Brain Chemistry / drug effects
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / physiology*
  • Haloperidol / pharmacology
  • Hydroxydopamines / pharmacology
  • Limbic System / drug effects
  • Limbic System / metabolism*
  • Male
  • Medial Forebrain Bundle / drug effects
  • Medial Forebrain Bundle / metabolism
  • Motor Activity / drug effects
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Oxidopamine
  • Pargyline / pharmacology
  • Rats
  • Stereotyped Behavior / drug effects
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism*

Substances

  • Azepines
  • Biogenic Monoamines
  • Hydroxydopamines
  • talipexole
  • Oxidopamine
  • Pargyline
  • Haloperidol
  • Apomorphine
  • Dopamine