Cain, D.

(1987) Kindling by Repeated Intraperitoneal or Intracerebral Injection of Picrotoxin

Transfers to Electrical Kindling. Experimental Neurology 97: 243-254.

1. Different routes of administration can yield very different, and at times opposite,
physiologic responses to the same drug due to the different pharmacokinetics that may
result. (Pag. 251; Rojo)

Adler, M. Rowan, C. and Geller, E. (1984) Intracerebroventricular Vs. Subcutaneous Drug

Administration: Apples and Oranges? Neuropetides 5: 73-76.

1. The longer it takes for a drug to reach its sites of actions, the greater the chance that it will
no longer be in its active form. (Pag 75; Rojo)

Jacquet, Y. (1980) Different Behavioral Effects Following Intracerebral, Intraventricular or

Intraperitoneal Injections of Naloxone in the Rat. Behavioral Brain Research 1: 543-546.

1. I.P route showed a decrease in behavioral activity, remaining immobile. (Pag 544; Verde)
2. I.C.V. animals showed a variable behavioral profile intermediate between that shown by
the Periaqueductal gray (PAG) and i.p. animals, with some animals showing behavioral
excitation and agitation, while others immobile but vigilant. (Pag 544; Naranja).
3. A high dose of naloxone exerted multiple actions depending on route of administration.
(Pag. 545; Amarillo).
4. The striking difference in behavior resulting from systemic or intracerebral PAG naloxone
may be due to a distribution factor – i.e. when naloxone is administered systemically, the
naloxone achieves distribution throughout the CNS, reaching sites other than the
morphine-sensitive PAG site. (Pag. 545; Azul)

Haley, T. and McCormick, W. (1957) Pharmacological Effects Produced by Intracerebral Injections

of Drugs in the Conscious Mouse. Brit. J. Pharmacol. 12: 12-15.

1. The mouse responses to drugs were, in main, similar to those in other species, including
human beings (Pag. 15; Rojo)
2. The rapidity of response after intracerebral injection preclude any direct action on the
peripheral receptors. (Pag. 15; Verde).

Urca, G. and Frenk, H. (1982) Systemic Morphine Blocks the Seizures Induced by
Intracerebroventricular (i.c.v.) Injections of Opiates and Opioid Peptides. Brain Research 246: 121-
126.

1. The second apparent paradox is the ability of the same opiate, morphine, to inhibit when
injected systemically its own epileptogenic action induced by intracereborventricular
injection (Pag. 124; Azul).
 2. Given such a differential distribution it may be that the opiates must act anatomically
different brain sites to exert either an epileptic or an antiepileptic effect (Pag. 124; Verde).
3. It may also be that the inhibitory and excitatory effects of opiates are due not only to their
action at anatomically distinct brain sites but also to the existence of different opiate
receptor within each site, differing in their affinities to the various opioid ligands, which
mediate the opposing effects of opiates (Pag. 124; Rojo).

Bevan, P., Brandshaw, C. and Szabadi, E. (1977) The Pharmacology of Adrenergic Neuronal
Responses in the Cerebral Cortex: Evidence for Excitatory alpha- and inhibitory beta-recepors.
Br. J. Pharmac. 59: 635-641.

1. It is well documented in periphery that the dose-response curve to IPNA (isoprenaline) is a

biphasic one: lower doses of the drug relax smooth muscle preparations due to the
stimulation of beta-receptors, whereas higher concentrations have a contractile effect due
to the activation of excitatory alpha-receptors (Pag. 638-640; Verde)