neuropeptide-y and phaclofen

This study examined the relationship between changes in GABA transmission and behavioral abnormalities after median nerve transection. Following unilateral median nerve transection, the percentage of GABA-like immunoreactive neurons in the cuneate nucleus and that of GABA(B) receptor-like immunoreactive neurons in the dorsal root ganglion in the injured side decreased and reached a nadir at 4 weeks after median nerve transection. Four weeks after bilateral median nerve transection and intraperitoneal application with saline, baclofen (2 mg kg⁻¹), or phaclofen (2 mg kg⁻¹) before unilateral electrical stimulation of the injured median nerve, we investigated the level of neuropeptide Y release and c-Fos expression in the stimulated side of the cuneate nucleus. The neuropeptide Y release level and the number of c-Fos-like immunoreactive neurons in the baclofen group were significantly attenuated, whereas those in the phaclofen group had increased compared to the saline group. These findings indicate that median nerve transection reduces GABA transmission, promoting injury-induced neuropeptide Y release and consequently evoking c-Fos expression in cuneate nucleus neurons. Furthermore, this study used the CatWalk method to assess behavioral abnormalities in rats following median nerve transection. These abnormalities were reversed by baclofen treatment. Overall, the results suggest that baclofen treatment block neuropeptide Y release, subsequently lessening c-Fos expression in cuneate neurons and consequently attenuating neuropathic signal transmission to the thalamus.

Topics: Animals; Baclofen; Electric Stimulation; GABA Antagonists; Gait; gamma-Aminobutyric Acid; Ganglia, Spinal; Male; Median Nerve; Median Neuropathy; Medulla Oblongata; Neuropeptide Y; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptors, GABA-B

The spinal regulation of cardiovascular sympathetic preganglionic neurons by substance P (SP) and gamma-aminobutyric acid (GABA) was investigated in conscious rats. Intrathecal injection at the T-9 spinal level of bicuculline, a GABAA receptor antagonist, evoked increases in mean arterial pressure (MAP) and heart rate (HR) which were maximal at 5.0 and 0.5 nmol, respectively. Phaclofen, a GABAB receptor antagonist, produced no cardiovascular changes up to 2 mumol while 10 mumol evoked a rise in MAP and HR. Muscimol, a GABAA receptor agonist, produced a decrease in MAP which was maximal at 5.0 nmol and had no effect on HR. Baclofen, a GABAB receptor agonist, was without cardiovascular effects up to 5.0 nmol, while 50 and 100 nmol evoked a fall in MAP and HR. The pressor response to SP (16.25 nmol, T-9) was antagonised by 0.5-50 nmol muscimol or baclofen in a dose-related manner and the pressor response to SP was still inhibited by 40 nmol GABA in capsaicin-treated animals. However, when SP was injected at T-2, the rise in both MAP and HR was blocked by 50 nmol baclofen. Similarly, 50 nmol muscimol blocked the rise in both MAP and HR induced by 15 nmol thyrotropin-releasing hormone. In contrast, 50 nmol glycine failed to alter the cardiovascular response to SP co-injected either at T-9 or T-2. Baclofen was found to reduce significantly the basal release of epinephrine when injected at the T-9 level. These results provide pharmacological evidence for a possible tonic GABAergic inhibitory input onto cardiovascular sympathetic preganglionic neurons mediated by GABAA and GABAB receptors.

Topics: Animals; Baclofen; Bicuculline; Blood Pressure; Capsaicin; Cardiovascular Physiological Phenomena; Cardiovascular System; Catecholamines; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid; Glycine; Heart Rate; Injections, Spinal; Male; Muscimol; Neurons; Neuropeptide Y; Rats; Rats, Inbred Strains; Receptors, GABA-A; Spinal Cord; Substance P; Sympathetic Nervous System