CHRONIC MORPHINE TREATMENT OF GUINEA-PIGS INDUCES NONSPECIFIC SENSITIVITY CHANGES IN THE NUCLEUS-TRACTUS-SOLITARIUS IN-VITRO

Chronic morphine treatment results inthe development of an opioid tole rance in guinea pig myenteric S-neurons that is nonspecific among phar macologically unrelated inhibitory agonists and the concurrent develop ment of a nonspecific super-sensitivity to unrelated excitatory agonis ts. The purpose of these studies was to extend this model of opioid to lerance in the guinea pig to central neurons, specifically to the medi al nucleus tractus solitarius (mnTS), the primary brainstem relay for visceroceptive information. Pharmacological responses of the guinea pi g mnTS neurons were examined in an in vitro brainstem slice preparatio n and compared between chronically morphine-treated animals and untrea ted controls. The spontaneous activity of guinea pig mnTS neurons was inhibited by gamma-aminobutyric acid (GABA), and GABA(A)-selective ago nist muscimol, 2-chloroadenosine and clonidine and was excited by glut amate and elevations in extracellular potassium. Applied along, morphi ne or the GABA(A)-selective antagonist bicuculline inhibited and excit ed approximately equal proportions of nucleus tractus solitarius (nTS) neurons. However, when applied in the presence of bicuculline, morphi ne inhibited most neurons tested. Reduced inhibitory responses to four agonists, i.e., morphine, muscimol, 2-chloroadenosine and clonidine, were observed in mnTS neurons in slices obtained from chronically morp hine-treated animals. Increased excitation of these neurons by elevate d extracellular potassium was observed. It is concluded that 1) guinea pig nTS neurons respond similarly to nTS neurons from other species i n vitro, 2) opioids disinhibit some proportion of guinea pig nTS neuro ns in vitor through a GABAergic mechanism and 3) the development of op ioid tolerance in guinea pig nTS neurons is qualitatively similar to t hat of guinea pig myenteric S-neurons.