Changes in benzodiazepine‐GABA receptor coupling in an accumbens‐habenula circuit after chronic diazepam treatment

Abstract

4 In general, the patterns of binding produced by the two different treatment routes were very similar. However, SR 95531 binding was lower in certain hippocampal fields in the i.p. treated animals compared to the rats implanted with silastic capsules. 5 It is concluded that repeated administration of diazepam evokes changes in benzodiazepine and GABA receptor coupling, and to a lesser extent changes in low affinity GABA binding, in certain interrelated brain structures of which an accumbens-habenula circuit is a central feature. These changes occur soon after the initiation of diazepam treatment, suggesting that they are unlikely to account for tolerance to the anxiolytic effects of diazepam but may trigger and/or accompany other critical neurochemical events.

A lack of tolerance to the anxiolytic effects of diazepam on the plus-maze: comparison of male and female rats

“…While evidence indicates that tolerance develops to the sedative/hypnotic, muscle relaxant and anticonvulsant properties of the benzodiazepines (File 1985;Rosenberg et al 1985), the data demonstrating tolerance to the anxiolytic effects of the benzodiazepines is inconsistent (Margules and Stein 1968;McMillan and Leander 1978;Vellucci and File 1979;Treit 1985a;Brett and Pratt 1995). Our results indicate that low-level continuous exposure to DZ does not induce tolerance to the anxiolytic effects of DZ, as measured by the elevated plusmaze.…”

“…Using anti-conflict tests, a lack of tolerance to the anxiolytic effect following chronic exposure to a variety of BZs has been shown (Margules and Stein 1968;Cook and Sepinwall 1975;McMillan and Leander 1978). More recent studies using the elevated plus-maze, conditioned defensive burying and the social interaction test have shown that chronic exposure reduces the anxiolytic effects of the BZs tested (Vellucci and File 1979;Stephens and Schneider 1985;Treit 1985b;File 1989aFile , 1989bIshihara et al 1993;Brett and Pratt 1995). These contradictions suggest that procedural differences and the behavioral test used to measure anxiety may affect the demonstration of tolerance following chronic benzodiazepine exposure.…”

“…Tolerance to DZ's anxiolytic effect was observed when animals were treated with 1 mg/kg/day for 21 days; however, tolerance was observed as early as 14 days when 2.5 mg/kg/day was used (File 1989a). In addition, behavioral tolerance has been observed with the silastic pellet implantation method of DZ exposure, although the anxiolytic effects following acute DZ exposure were undetectable from controls in that study (Brett and Pratt 1995).…”

Differential Effects of Two Chronic Diazepam Treatment Regimes on Withdrawal Anxiety and AMPA Receptor Characteristics

“…Moreover, common structures were activated during withdrawal (Laurie and Pratt, 1993). Despite these brain structures displaying changes in functional activity Pratt, 1989, 1993), they did not exhibit alterations in GABA A receptor binding properties in complementary receptor autoradiography studies (Brett and Pratt, 1995). These studies do not however rule out the possibility that changes in GABA A receptor subunit gene expression may confer alterations in GABA A receptor function in BZ dependence.…”

Subchronic treatment with antiepileptic drugs modifies pentylenetetrazol-induced seizures in mice: Its correlation with benzodiazepine receptor binding

“…Chronic administration of BDZ can produce decreased sensitivity to GABA (Gallager et al 1984) and reduced ability of this amino acid to enhance BDZ binding (Brett and Pratt 1995). Indeed, withdrawal symptoms or spontaneous seizures have been reported to occur in nonepileptic BDZ abusers upon drug discontinuation (Lukas and Griffith 1984).…”