Cholinergic and GABAergic modulation of self-stimulation of lateral hypothalamus and ventral tegmentum: effects of carbachol, atropine, bicuculline, and picrotoxin.
This study aimed at investigating the effects of modulators of acetylcholine-muscarinic (ACh-M) and GABAA.B-receptors in the lateral hypothalamus and ventral tegmentum on the electrical self-stimulation evoked from these regions. In each Wistar rat, a bipolar electrode and an ipsilateral insulated cannula-cum-electrode were implanted chronically in the right hemisphere. There were two placement combinations: 1. Bipolar electrode in lateral hypothalamus-medial forebrain bundle (LH-MFB) and cannulacum-electrode in ventral tegmental area-substantia nigra (VTA-SN) or 2, bipolar electrode in VTA-SN and cannula-cum-electrode in LH-MFB. The stimulation parameters were kept at a level to obtain 50% of the maximum possible asymptotic intracranial self-stimulation (ICSS) rates (M50) from each site. Carbachol injected into VTA-SN increased the ICSS responding rate of VTA-SN as well as, indirectly, that of LH-MFB, and atropine injections had an opposite effect. Similar injections of these ligands into LH-MFB again had facilitatory and inhibitory effects on its ICSS: however, there was no indirect effect on the ICSS of VTA-SN. Bicuculline injection into VTA-SN had no effect on either its ICSS or that of LH-MFB. On the other hand, bicuculline injected into LH-MFB decreased its ICSS and, indirectly, the ICSS of VTA-SN in a dose-dependent manner. In contrast, intra VTA-SN injections of picrotoxin decreased its ICSS and, indirectly, ICSS of LH-MFB. Similar injections into LH-MFB had no effect on the ICSS of VTA-SN. The results suggest that ICSS of VTA-SN is Ach-M receptor mediated and, also, this mediation influences the ICSS of LH-MFB. On the contrary, changes in ICSS of LH-MFB following Ach-M receptor ligands do not influence the ICSS of VTA-SN. The direct effects of GABA-receptor antagonists have shown disassociation because ICSS of LH-MFB was more sensitive to bicuculline, whereas the ICSS of VTA-SN was more sensitive to picrotoxin. Thus, the cholinergic and GABAergic mechanisms of the self-stimulation of lateral hypothalamus and ventral tegmentum are different.
Singh
J
J
Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Desiraju
T
T
Raju
T R
TR
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D018756:GABA Antagonists / Q000494:pharmacology; D007026:Hypothalamic Area, Lateral / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008845:Microinjections; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D012653:Self Stimulation / Q000187:drug effects* / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D001285:Atropine; D001640:Bicuculline; D002217:Carbachol; D018756:GABA Antagonists; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010852:Picrotoxin; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic