Anxiolytic Properties of Opiates and Endogenous Opioid Peptides and Their Relationship to the Actions of Benzodiazepines1

The Endomorphin System and Its Evolving Neurophysiological Role

“…Anxiety. There are several reports on the anxiolytic action of morphine and -opioid receptor agonists, injected both centrally (File and Rodgers, 1979;Fanselow et al, 1988;Costall et al, 1989;Motta et al, 1995) and peripherally (Millan and Duka, 1981;Koks et al, 1999;Zarrindast et al, 2005), and the anxiogenic effect produced by -opioid receptor antagonists (Tsuda et al, 1996). The effects of morphine are dose-and site-dependent: morphine injected into the midbrain tectum of rats at low doses produced anxiolytic-like effects, but at high doses displayed an anxiogenic-like activity (Brandao et al, 1999); when injected to the rat dorsal PAG and lateral septum (Le Merrer et al, 2006), morphine produced dose-dependent aversive effects.…”

Overexpression of Proenkephalin in the Amygdala Potentiates the Anxiolytic Effects of Benzodiazepines

“…Preproenkephalin knockout (Konig et al 1996), and some novel -opioid agonists show anxiolytic properties (Privette and Terrian 1995). Several lines of evidence also indicate the involvement of endogenous opioid peptides in various aspects of benzodiazepine action, including their influences on food intake, locomotor activity, conflict, and anxiety-like behaviors (Millan and Duka 1981;Cooper 1983;Nowakowska and Chodera 1990). Interestingly, clinical studies suggest interactions between responses to benzodiazepines and opioids in humans (Darke et al 1993).…”

Endorphinergic Systems and the Response to Stress

“…49, 50, 54], The ability of dexamethasone treatment, but not neurointermediolobotomy, to selectively decrease grooming behaviour is suggestive of a role of AL P-EP in this phenomenon [54], A role of EOPs in mediating reward, arousal and drive, a direct stimulatory effect upon motor activity and an anxiolytic action (see below) are mechanisms which could underlie the influence which EOPs exert upon behaviour in the circumstances of novelty stress [49,50], It should be emphasized that these effects of naloxone are not manifested in animals familiar with their environment: its influence is thus peculiar to the presence of stress [49,50,54],…”

“…Morphine has, moreover, been often found to act positively in tests employed for the screening of anxio lytic drugs and naloxone shown to block the anxiolytic actions of benzodi azepines in the conflict test [e.g. 15,31,46,50,66], EOPs may, thus, mediate the anxiolytic actions of these minor tranquillizers. Finally, opiates (applied intraccrebroventricularly or systematically) decrease, whereas nal oxone enhances the motor agitation and distress vocalizations emitted by young vertebrates separated from their parents [49,50].…”

“…15,31,46,50,66], EOPs may, thus, mediate the anxiolytic actions of these minor tranquillizers. Finally, opiates (applied intraccrebroventricularly or systematically) decrease, whereas nal oxone enhances the motor agitation and distress vocalizations emitted by young vertebrates separated from their parents [49,50]. This is an action shared with imipraminc in dogs and the benzodiazepines in chicks and is thus evidential of an antidepressant-like, in addition to an anxiolytic-like role of EOPs in the regulation of emotionality under stress.…”